Synthesis and Insecticidal/Fungicidal Activities of Triazone Derivatives Containing Acylhydrazone Moieties

Peipei Cui; Yan Yang

doi:10.3390/molecules30020340

. 2025 Jan 16;30(2):340. doi: 10.3390/molecules30020340

Synthesis and Insecticidal/Fungicidal Activities of Triazone Derivatives Containing Acylhydrazone Moieties

Peipei Cui ¹, Yan Yang ^2,^*

Editor: Josphat Matasyoh

PMCID: PMC11767570 PMID: 39860209

Abstract

A series of novel triazone derivatives containing aldehyde hydrazone or ketone hydrazone moieties were designed, synthesized and their biological activities were investigated against Aphis craccivora, Culex pipiens pallens, Helicoverpa armigera, Ostrinia nubilalis, Mythimna separata and 14 Kinds of fungi. Most of the aldehyde hydrazone exhibited excellent insecticidal activities against A. craccivora. In particular, the aphicidal activities of compounds 3t (35%) and 3w (30%) were equivalent to pymetrozine (30%) at 5 mg/kg. The aphicidal activities of derivatives 3p, 3u, 3y, 5g, 5i, 5l, 5q and 5u against C. pipiens pallens were higher than that of pymetrozine. Compound 3u (100%) exhibited good larvicidal activities against C. pipiens pallens at 0.25 mg/kg. Most derivatives exhibited broad-spectrum fungicidal activities against 14 kinds of plant fungi at 50 mg/kg. Thirty-nine compounds exhibited a more than 50% inhibition rate against Physalospora piricola. Compounds 3h, 3t and 3w were expected to be the leading structure for the development of new triazone insecticides agents.

Keywords: triazone, hydrazone, biological activities

1. Introduction

Owing to their direct feeding, transmission of destructive plant viruses and high reproductive rate [1], aphids (Hemiptera: Aphididae) have become the most destructive pests, causing plant diseases that significantly reduce crop yield and quality [2].

As a pyridine azomethine insecticide, pymetrozine was first developed by Syngenta in 1988 [3] and has become a hot research topic globally due to its high efficiency, satisfied selectivity and environmental friendliness [4,5,6,7,8,9,10,11,12,13,14]. However, only two analogs of this type of insecticides (R-768 and pyrifluquinazon (Figure 1)) have been found so far, and their activities were significantly lower than that of pymetrozine [9,15].

In 2015, Nesterov et al. found that the action targets of pymetrozine insecticide were transient receptor potential (TRP) channels [16], which were non-selective cation channels composed of 28 cation-permeable channels. TRPC (transient receptor potential-canonical) was a subfamily of TRP channels [17], which was inwardly rectifying and was considered as a therapeutic target for mental disorders such as depression, borderline personality disorder and post-traumatic stress disorder [18,19]. The pyridazinone compound GFB-8438 (Figure 2) was a highly selective, potent TRPC5 antagonist, which specifically interacted with the TRPC5-Rac1 pathway in podocytes to attenuate FSGS and diabetic nephropathy [20]. Pymetrozine acted on the same target site as GFB-8438 [16].

Selected TRP antagonists, pesticides and drugs containing hydrazones moieties. The hydrazone structure is marked with different colors. For compounds with proprietary names, proprietary names are used. For compounds without proprietary names, numbers are used.

Hydrazones moieties are important structural units that exist in many bioactive molecules, with a wide range of biological activities. Metaflumizone is a semicarbazone insecticide developed by BASF (Ludwigshafen, Germany) and Nihon Nohyaku Co., Ltd. (Tokyo, Japan) which provides good-to-excellent control of lepidopterous pests and certain pests in the orders Coleoptera, Hemiptera, Hymenoptera, Diptera, Isoptera and Siphonaptera [21]. Diflufenzopyr containing hydrazone moiety is also used as a commercialized insecticide [22]. Benquinox is a desirable fungicide which protects seeds and seedlings against fungal infections [23]. Furacilin has been used for the treatment of bacterial and protozoal infections for many years [24]. Compounds 3 [25] and 4 [26] exhibit higher antiviral activities than ribavirin. Azimilide and Ftivazide exhibit antiarrhythmic [27] and antituberculosis [28] activities, respectively. GFB-887 [29] compounds 1 and 2 [30] (Figure 2) containing hydrazone moieties were used as TRP antagonists. Based on the bioactivies and targeting TRP channels of GFB-8438, GFB-887, 1 and pymetrozine, the acylhydrazone structure was introduced into pymetrozine to design and synthesize a series of triazone aldehyde and ketone hydrazone derivatives (Figure 3). Their insecticidal activities against bean aphid and lepidopteran pests were repeated three times. In addition, their antiphytopathogenic fungus activities were also investigated.

Design of target compounds. The hydrazone structure is marked with different colors. For compounds with proprietary names, proprietary names are used. For compounds without proprietary names, numbers are used.

2. Results and Discussions

2.1. General Synthesis

The synthetic routes of the target compounds 3a–3w and 5a–5u are given in Scheme 1. Intermediate 1 was synthesized by the method reported in the literature [31]. 4-Amino-6-methyl-4,5-dihydro-2H-[1,2,4]triazin-3-one reacted with benzoyl chloride to give (6-Methyl-3-oxo-2,5-dihydro-3H-[1,2,4]triazin-4-yl)-carbamic acid phenyl ester, which reacted with hydrazine hydrate to give intermediate 1. Using p-toluenesulfonic acid as a catalyst, compound 1 reacted with aldehydes 2a–2w to form compounds 3a–3w in 57–88% yields. Compounds 5a–5u were synthesized by the condensation of compound 1 and ketones 4a–4u in 56–97% yields. Alkyl, cycloalkyl, and substituted phenyl were introduced into acylhydrazone derivatives to investigate the effect of different substituents on activity. Experimental operating steps and data of target compounds 3a–3w and 5a–5u are available in the Supplementary Materials.

2.2. Biological Evaluation

2.2.1. Foliar Contact Activity Against Bean Aphid (A. craccivora)

As seen from Table 1, most aldehyde hydrazone compounds exhibited weak insecticidal activities; only compounds 3h (2, 3-dimethoxy, 15%), 3t (4-dimethylamino, 35%) and 3w (2-thiophene, 30%) exhibited the same level of aphicidal activities as pymetrozine (30%) at 5 mg/kg. Compounds 3t and 3w exhibited high insecticidal activities because nitrogen and sulfur atoms may form hydrogen bonding with the TRP channels [16]. The rotation of chemical bonds of acylhydrazone compounds can lead to different conformations [32], also affecting their biological activities.

Table 1.

Foliar contact activities against A. craccivora of compounds 3a–3w and pymetrozine.

Compound	R₁	Correcting Mortality (%) at Concentration (mg/kg)
Compound	R₁	600	100	10	5
3a		70 ± 2	30 ± 0	-^a	-^a
3b		100 ± 0	85 ± 2	30 ± 0	-^a
3c		100 ± 0	70 ± 1	-^a	-^a
3d		100 ± 0	95 ± 2	30 ± 0	-^a
3e		100 ± 0	90 ± 0	30 ± 0	-^a
3f		100 ± 0	70 ± 0	20 ± 0	-^a
3g		100 ± 0	95 ± 2	45 ± 2	-^a
3h		100 ± 0	100 ± 0	70 ± 0	15 ± 1
3i		95 ± 1	90 ± 0	50 ± 0	-^a
3j		100 ± 0	100 ± 0	40 ± 0	-^a
3k		100 ± 0	95 ±2	30 ± 0	-^a
3l		100 ± 0	95 ± 2	35	-^a
3m		100 ± 0	100 ± 0	40 ± 0	-^a
3n		100 ± 0	90 ± 0	30 ± 0	-^a
3o		100 ± 0	95 ± 0	35 ± 0	-^a
3p		85 ± 2	40 ± 0	-^a	-^a
3q		100 ± 0	90 ± 0	35 ± 1	-^a
3r		100 ± 0	80 ± 0	20 ± 0	-^a
3s		100 ± 0	90 ± 0	25 ± 2	-^a
3t		100 ± 0	100 ± 0	95 ± 0	35 ± 2
3u		100 ± 0	90 ± 0	30 ± 0	-^a
3v		100 ± 0	95 ± 0	45 ± 0	-^a
3w		100 ± 0	100 ± 0	85 ± 2	30 ± 0
pymetrozine		100 ± 0	100 ± 0	90 ± 0	30 ± 0

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^a-not tested.

When R was an alkyl substituent, the size of the substituent had significant effects on the aphicidal activities (3a–3c). For example, the insecticidal activity of compound 3b (85%, t-butyl) was higher than that of compound 3a (30%, n-propyl) at 100 mg/kg. When R was aromatic groups, the activities increased obviously. In order to investigate the effects of the substituent positions, electrical properties and the number of substituents on the phenyl group on the insecticidal activities, different substituents were introduced to the benzene ring (3e–3t). The results indicated that most of these derivatives exhibited more than 30% activity at 10 mg/kg, which was lower than that of pymetrozine (90%). The positions and numbers of electron-donating substituents had important effects on the activities; for example, compounds 3f (3-methoxy, 20%) and 3g (4-methoxy, 45%) exhibited lower activities than 3h (2, 3-dimethoxy, 70%) at 10 mg/kg. The positions and numbers of electron-withdrawing substituents had little effect on the activities; for example, 3l (3-chlorine, 35%) and 3m (4-chlorine, 40%) exhibited activities which were equivalent to 3n (3, 4-dichlorine, 30%) at 10 mg/kg. Meanwhile, it was found that the electron-donating compound 3t (4-dimethylamino, 35%) and electron-withdrawing compound 3w (2-thiophene, 30%) exhibited activities which were equivalent to pymetrozine (30%) at 5 mg/kg.

When R was changed from phenyl to naphthyl, the insecticidal activity of the compound remained unchanged; such as in compound 3d (phenyl, 30%), which exhibited activity equivalent to 3u (naphthyl, 30%) at 10 mg/kg. In addition, while the benzene ring was replaced with other aromatic heterocycles (3v–3w), the insecticidal activities were enhanced. For example, compound 3w (2-thiophene, 30%) exhibited the same level of activity as pymetrozine (30%) at 5 mg/kg.

The aphicidal activities of ketone hydrazone derivatives (5a–5u) are listed in Table 2. From Table 1 and Table 2, it can be seen that most aldehyde hydrazone derivatives exhibited better activities than the ketone hydrazone compounds.

Table 2.

Foliar contact activities against A. craccivora of compounds 5a–5u and pymetrozine.

Compound	R₂	Correcting Mortality (%) at Concentration (mg/kg)
Compound	R₂	600	100	10	5
5a		90 ± 0	30 ± 0	-^a	-^a
5b		100 ± 0	35 ± 2	-^a	-^a
5c		100 ± 0	40 ± 0	-^a	-^a
5d		95 ± 2	70 ± 0	15 ± 1	-^a
5e		80 ± 0	45 ± 2	-^a	-^a
5f		80 ± 0	30 ± 0	-^a	-^a
5g		95 ± 2	60 ± 0	10 ± 0	-^a
5h		100 ± 0	50 ± 0	-^a	-^a
5i		100 ± 0	65 ± 1	10 ± 0	-^a
5j		100 ± 0	80 ± 0	35 ± 2	-^a
5k		100 ± 0	95 ± 2	65 ± 2	-^a
5l		95 ± 2	80 ± 0	10 ± 0	-^a
5m		100 ± 0	70 ± 0	10 ± 0	-^a
5n		90 ± 0	30 ± 0	-^a	-^a
5o		100 ± 0	75 ± 2	15 ± 1	-^a
5p		95 ± 1	85 ± 0	25 ± 1	-^a
5q		100 ± 0	95 ± 0	45 ± 0	-^a
5r		100 ± 0	80 ± 0	25 ± 0	-^a
5s		100 ± 0	95 ± 0	35 ± 0	-^a
5t		100 ± 0	85 ± 0	35 ± 1	-^a
5u		100 ± 0	90 ± 0	35 ± 1	-^a
pymetrozine		100 ± 0	100 ± 0	90 ± 0	30 ± 0

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^a—not tested.

2.2.2. Larvicidal Activities Against Mosquito (C. pipiens pallens), Cotton Bollworm (H. armigera), Oriental Armyworm (M. separata) and Corn Borer (O. nubilalis)

The larvicidal activities of synthesized compounds 3a–3w, 5a–5u and pymetrozine against mosquitoes are shown in Table 3 and Table 4. Most compounds exhibited good larvicidal activities against C. pipiens pallens. In particular, the larvicidal activities of derivatives 3p, 3u, 3y, 5g, 5i, 5l, 5q and 5u were higher than that of pymetrozine, and compound 3u (containing a 6-methoxy on the naphthyl) showed the highest larvicidal activity (40% at 0.1 mg/kg). The positions and numbers of substituents on the phenyl of these derivatives were critical for the activities against mosquitoes. For example, 5h (3-methoxy) only showed 20% correcting mortality at 0.5 mg/kg, whereas 5i (4-methoxy) exhibited 40% correcting mortality at 0.25 mg/kg. Meanwhile, 5j (3,4-diemethoxy) and 5k (3,4,5-triemethoxy) exhibited 50% and 30% correcting mortality at 0.5 mg/kg, respectively.

Table 3.

Insecticidal activities of compounds 3a–3w, 5a–5u and pymetrozine against C. pipiens pallens.

Compound	Correcting Mortality (%) at Concentration (mg/kg)
Compound	10	5	2	1	0.5	0.25	0.1
3a	30 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
3b	100 ± 0	0	-^a	-^a	-^a	-^a	-^a
3c	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a	-^a	-^a
3d	40 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
3e	100 ± 0	100 ± 0	50 ± 0	-^a	-^a	-^a	-^a
3f	100 ± 0	100 ± 0	60 ± 0	-^a	-^a	-^a	-^a
3g	100 ± 0	100 ± 0	40 ± 0	-^a	-^a	-^a	-^a
3h	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a	-^a	-^a
3i	100 ± 0	40 ± 0	-^a	-^a	-^a	-^a	-^a
3j	100 ± 0	100 ± 0	100 ± 0	100 ± 0	60 ± 0	-^a	-^a
3k	100 ± 0	20 ± 0	-	-	-	-^a	-^a
3l	100 ± 0	100 ± 0	100 ± 0	100 ± 0	60 ± 0	-^a	-^a
3m	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a	-^a
3n	100 ± 0	100 ± 0	70 ± 0	-^a	-^a	-^a	-^a
3o	80 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
3p	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a
3q	100 ± 0	100 ± 0	20 ± 0	-^a	-^a	-^a	-^a
3r	100 ± 0	100 ± 0	100 ± 0	100 ± 0	60 ± 0	-^a	-^a
3s	100 ± 0	100 ± 0	10 ± 0	-^a	-^a	-^a	-^a
3t	30 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
3u	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0
3v	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a
3w	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a	-^a
5a	100 ± 0	100 ± 0	40 ± 0	-^a	-^a	-^a	-^a
5b	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a	-^a
5c	50 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
5d	30 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
5e	30 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
5f	60 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
5g	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a
5h	100 ± 0	100 ± 0	100 ± 0	80 ± 0	20 ± 0	-^a	-^a
5i	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a
5j	100 ± 0	100 ± 0	100 ± 0	100 ± 0	50 ± 0	-^a	-^a
5k	100 ± 0	100 ± 0	100 ± 0	100 ± 0	30 ± 0	-^a	-^a
5l	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a
5m	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a	-^a
5n	100 ± 0	100 ± 0	100 ± 0	100 ± 0	60 ± 0	-^a	-^a
5o	100 ± 0	100 ± 0	100 ± 0	100 ± 0	100 ± 0	40 ± 0	-^a
5p	100 ± 0	100 ± 0	100 ± 0	60 ± 0	-^a	-^a	-^a
5q	100 ± 0	100 ± 0	100 ± 0	80 ± 0	20 ± 0	-^a	-^a
5r	80 ± 0	40 ± 0	-^a	-^a	-^a	-^a	-^a
5s	90 ± 0	30± 0	-^a	-^a	-^a	-^a	-^a
5t	70 ± 0	-^a	-^a	-^a	-^a	-^a	-^a
5u	100 ± 0	100 ± 0	100 ± 0	100 ± 0	20 ± 0	-^a	-^a
pymetrozine	100 ± 0	40 ± 0	-^a	-^a	-^a	-^a	-^a

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^a—not tested.

Table 4.

Insecticidal activities of compounds 3a–3w, 5a–5u and pymetrozine against H. armigera, O. nubilalis and M. separata at 600 mg/kg.

Compound	Correcting Mortality (%) at Concentration 600 mg/kg mg/kg)
Compound	H. armigera	O. ubilalis	M. eparata
3a	15 ± 0	15 ± 0	10 ± 0
3b	0	0	5 ± 0
3c	25 ± 0	15 ± 0	20 ± 0
3d	15 ± 0	10 ± 0	20 ± 0
3e	5 ± 0	20 ± 0	20 ± 0
3f	15 ± 0	5 ± 0	15 ± 0
3g	0	0	0
3h	20 ± 0	15 ± 0	25 ± 0
3i	0	0	5 ± 0
3j	25 ± 0	15 ± 0	25 ± 0
3k	10 ± 0	5 ± 0	20 ± 0
3l	55 ± 0	45 ± 0	70 ± 0
3m	15 ± 0	10 ± 0	20 ± 0
3n	55 ± 0	45 ± 0	65 ± 0
3o	0	0	5 ± 0
3p	100 ± 0/100 ^a ± 0/ 20^b ± 0	100 ± 0/100 ^a ± 0/30 ^b ± 0	100 ± 0/100 ^a ± 0/20 ^b ± 0
3q	25 ± 0	20 ± 0	35 ± 0
3r	35 ± 0	25 ± 0	45 ± 0
3s	10 ± 0	20 ± 0	20 ± 0
3t	100 ± 0/100 ^a ± 0/30 ^b ± 0	100 ± 0/100 ^a ± 0/20 ^b ± 0	100 ± 0/100 ^a ± 0/60 ^b ± 0
3u	15 ± 0	10 ± 0	15 ± 0
3v	15 ± 0	10 ± 0	25 ± 0
3w	35 ± 0	25 ± 0	40 ± 0
5a	15 ± 0	10 ± 0	25 ± 0
5b	55 ± 0	50 ± 0	80 ± 0
5c	20 ± 0	10 ± 0	20 ± 0
5d	0	0	0
5e	15 ± 0	10 ± 0	20 ± 0
5f	50 ± 0	45 ± 0	65 ± 0
5g	20 ± 0	15 ± 0	25 ± 0
5h	35 ± 0	20 ± 0	25 ± 0
5i	55 ± 0	50 ± 0	65 ± 0
5j	25 ± 0	30 ± 0	10 ± 0
5k	10 ± 0	25 ± 0	15 ± 0
5l	50 ± 0	40 ± 0	60 ± 0
5m	0	0	5 ± 0
5n	20 ± 0	15 ± 0	30 ± 0
5o	55 ± 0	45 ± 0	65 ± 0
5p	20 ± 0	25 ± 0	25 ± 0
5q	30 ± 0	15 ± 0	15 ± 0
5r	0	0	5 ± 0
5s	30 ± 0	25 ± 0	15 ± 0
5t	20 ± 0	15 ± 0	20 ± 0
5u	20 ± 0	10 ± 0	20 ± 0
pymetrozine	20 ± 0	40 ± 0	50 ± 0

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^a Mortality at 200 mg/L, ^b Mortality at 100 mg/L.

Compounds 3a–3w and 5a–5u have high stability. According to previous research on compounds with similar structures, compounds 3a–3w and 5a–5u may exhibit lower toxicity to non-target organisms. Compounds with higher nitrogen atom ratios may have relatively higher acute toxicity. Therefore, we predict that compounds 3t, 3p, 3q, 3v and 5u may exhibit relatively higher toxicity. Therefore, compounds 3t and 3w can be further developed as potential insecticides.

2.2.3. Fungicidal Activities

Compounds 3a–3w and 5a–5u were also evaluated for their fungicidal activities, with commercial fungicides carbendazim and chlorothalonil as controls (Table 5). The fungicidal activities test was repeated three times. Most derivatives showed broad-spectrum fungicidal activities against 14 kinds of phytopathogens. Overall, these derivatives showed excellent fungicidal activities against P. piricola. In particular, compound 5l exhibited more than 50% inhibition against six kinds of fungi; compounds 5c, 5f and 5g exhibited more than 50% inhibition against five kinds of fungi and compound 5t exhibited a 90% inhibition rate against P. piricola at 50 mg/kg. The fungicidal activities of these compounds also exhibited a certain selectivity. At 50 mg/kg, 20 compounds exhibited a more than 50% inhibition rate against Fusarium graminearum, which was higher than chlorothalonil. A total of 7 compounds (against Fusarium oxysporum f. sp. cucumeris), 19 compounds (against Cercospora arachidicola Hori), 39 kinds of compounds (against P. piricola) and 13 compounds (against Fusarium moniliforme) showed a more than 50% inhibition rate at the concentration of 50 mg/kg, which was higher than the fungicidal activities of carbendazim.

Table 5.

In vitro fungicidal activities of compounds 3a–3w, 5a–5u, carbendazim and chlorothalonil against 14 kinds of fungi.

Compound	Fungicidal Activities (%) ^a at 50 mg/kg
Compound	AS ^b	FG ^b	PI ^b	PC ^b	SS ^b	BC ^b	RS ^b	FC ^b	CH ^b	PP ^b	RC ^b	BM ^b	WA ^b	FM ^b
3a	33 ± 1	13 ± 1	4 ± 1	14 ± 1	11 ± 1	12 ± 1	28 ± 1	8 ± 3	0	21 ± 1	18 ± 1	42 ± 2	27 ± 2	11 ± 1
3b	6 ± 1	11 ± 2	11 ± 1	23 ± 1	13 ± 1	7 ± 3	17 ± 2	47 ± 2	42 ± 3	86 ± 3	79 ± 1	35 ± 1	47 ± 1	58 ± 1
3c	9 ± 2	38 ± 1	14 ± 2	27 ± 2	37 ± 1	18 ± 1	22 ± 2	55 ± 1	60 ± 1	85 ± 1	85 ± 1	55 ± 2	39 ± 1	53 ± 1
3d	31 ± 3	26 ± 1	19 ± 1	37 ± 3	25 ± 1	5 ± 1	36 ± 1	12 ± 1	0	37 ± 2	38 ± 2	25 ± 1	27 ± 3	19 ± 1
3e	21 ± 1	26 ± 1	12 ± 1	20 ± 2	11 ± 1	11 ± 1	8 ± 2	6 ± 1	25 ± 1	72 ± 1	58 ± 1	25 ± 1	20 ± 2	21 ± 1
3f	12 ± 1	76 ± 1	9 ± 2	10 ± 1	25 ± 3	5 ± 1	43 ± 2	35 ± 1	50± 1	65 ± 2	68 ± 1	35 ± 1	52 ± 2	38 ± 1
3g	31 ± 2	30 ± 1	9 ± 1	10 ± 1	20 ± 2	10 ± 2	33 ± 1	45 ± 1	56 ± 1	73 ± 3	79 ± 1	65 ± 1	39 ± 1	20 ± 1
3h	6 ± 1	38 ± 1	14 ± 1	34 ± 2	37 ± 3	36 ± 2	57 ± 2	42 ± 2	44 ± 1	60 ± 2	71 ± 1	30 ± 2	32 ± 1	36 ± 1
3i	12 ± 1	38 ± 2	4 ± 2	24 ± 1	25 ± 3	13 ± 1	45 ± 2	32 ± 1	42 ± 3	65 ± 1	42 ± 1	40 ± 1	44 ± 2	48 ± 1
3j	12 ±2	69 ± 1	14 ± 1	10 ± 1	13 ± 2	13 ± 1	26 ± 1	35 ± 1	39 ± 1	57 ± 1	56 ± 2	47 ± 1	41 ± 2	38 ± 1
3k	6 ± 1	57 ± 2	14 ± 1	41 ± 1	15 ± 1	2 ± 2	33 ± 1	32 ± 2	57 ± 1	70 ± 1	49 ± 1	47 ± 1	33 ± 1	32 ± 1
3l	12 ± 2	30 ± 2	4 ± 1	6 ± 3	29 ± 1	23 ± 2	40 ± 1	45 ± 1	48 ± 1	77 ± 1	72 ± 2	42 ± 1	25 ± 1	50 ± 1
3m	12 ± 2	73 ± 1	14 ± 1	13 ± 2	15 ± 1	5 ± 1	14 ± 1	32 ± 2	46 ± 1	54 ± 1	60 ± 1	42 ± 1	44 ± 1	38 ± 2
3n	18 ± 1	11 ± 1	9 ± 2	37 ± 2	20 ± 2	18 ± 1	45 ± 2	32 ± 2	44 ± 1	52 ± 1	49 ± 1	47 ± 2	25 ± 1	46 ± 2
3o	25 ± 1	61 ± 1	19 ± 1	17 ± 1	20 ± 2	7 ± 3	24 ± 2	45 ± 1	50 ± 1	72 ± 1	62 ± 2	40 ± 1	30 ± 2	45 ± 1
3p	18 ± 1	50 ± 1	14 ± 1	44 ± 1	15 ± 1	18 ± 1	19 ± 1	27 ± 1	50 ± 1	60 ± 2	56 ± 1	47 ± 2	41 ± 3	41 ± 3
3q	12 ± 2	50 ± 1	14 ± 1	37 ± 1	34 ± 1	10 ± 2	10 ± 2	30 ± 1	56 ± 1	73 ± 3	74 ± 1	42 ± 2	39 ± 1	46 ± 2
3r	6 ± 1	34 ± 1	23 ± 2	34 ± 1	17 ± 1	13 ± 1	22 ± 2	22 ± 1	32 ± 1	65 ± 2	50 ± 1	12 ± 2	0	16 ± 1
3s	6 ± 2	25 ± 2	16 ± 2	35 ± 1	17 ± 3	25 ± 2	26 ± 2	32 ± 2	35 ± 2	56 ± 1	58 ± 1	42 ± 1	31 ± 1	15 ± 1
3t	12 ± 1	51 ± 1	4 ± 1	10 ± 1	27 ± 2	31 ± 2	54 ± 1	35 ± 1	50 ± 1	78 ± 2	62 ± 1	47 ± 2	52 ± 2	41 ± 3
3u	12 ± 1	34 ± 2	4 ± 1	17 ± 1	24 ± 1	5 ± 1	40 ± 1	35 ± 1	44 ± 1	72 ± 1	72 ± 3	35 ± 1	39 ± 1	33 ± 1
3v	17 ± 2	11 ± 1	11.8	11 ± 1	11 ± 2	7 ± 2	15 ± 1	47 ± 2	57 ± 1	83 ± 2	78 ± 1	60 ± 1	55 ± 2	58 ± 1
3w	5 ± 1	17 ± 2	8 ± 3	11 ± 1	16 ± 1	7 ± 2	13 ± 1	47 ± 2	50 ± 1	78 ± 2	78 ± 1	40 ± 1	27 ± 2	41 ± 3
5a	18 ± 3	61 ± 1	23 ± 1	41 ± 1	10 ± 1	5 ± 1	22 ± 3	47 ± 1	48 ± 2	78 ± 2	71 ± 2	32 ± 2	35 ± 2	40 ± 1
5b	18 ± 1	11 ± 2	4 ± 2	17 ± 1	15 ± 2	10 ± 2	49 ± 1	60 ± 1	60 ±2	80 ± 1	82 ± 2	57 ± 2	42 ± 2	46 ± 2
5c	18 ± 1	73 ± 1	14 ± 1	10 ± 1	25 ± 3	13 ± 1	24 ± 2	60 ± 1	56 ± 2	82 ± 1	84 ± 1	50 ± 1	42 ± 2	53 ± 1
5d	25 ± 2	76 ± 2	14 ± 1	31 ± 1	24 ± 1	10 ± 1	42 ± 1	45 ± 2	44 ± 1	85 ± 1	86 ± 1	57 ± 1	50 ± 1	56 ± 1
5e	12 ± 1	73 ± 3	4 ± 2	27 ± 2	34 ± 1	26 ± 1	45 ± 1	45 ± 1	44 ± 1	72 ± 1	82 ± 2	52 ± 1	35 ± 1	56 ± 1
5f	25 ± 1	73 ± 2	33 ± 1	31 ± 1	29 ± 1	31 ± 2	22 ± 2	51 ± 1	56 ± 1	65 ± 2	67 ± 3	55 ± 1	39 ± 1	56 ± 1
5g	18 ± 2	57 ± 2	14 ± 1	10 ± 1	15 ± 1	10 ± 1	49 ± 1	52 ± 2	52 ± 1	70 ± 2	71 ± 1	60 ± 1	42 ± 2	63 ± 1
5h	18 ± 1	26 ± 3	9 ± 1	17 ± 1	16 ± 1	16 ± 1	16 ± 1	42 ± 1	49 ± 1	54 ± 1	59 ± 1	42 ± 1	34 ± 1	37 ± 1
5i	18 ± 1	53 ± 1	9 ± 2	31 ± 1	37 ± 3	13 ± 1	10 ± 1	47 ± 2	52 ± 1	86 ± 2	80 ± 1	57 ± 2	57 ± 1	56 ± 2
5j	12 ± 1	44 ± 2	11 ± 1	11 ± 2	23 ± 2	24 ± 1	31 ± 1	47 ± 2	45 ± 2	49 ± 1	54 ± 2	39 ± 1	38 ± 2	27 ± 2
5k	17 ± 2	52 ± 1	15 ± 3	10 ± 2	17 ± 1	6 ± 1	24 ± 3	50 ± 1	53 ± 1	42 ± 1	52 ± 1	47 ± 1	39 ± 1	23 ± 1
5l	50 ± 1	61 ± 2	23 ± 3	17 ± 1	24 ± 1	5 ± 1	28 ± 1	57 ± 2	52 ± 1	75 ± 1	59 ± 1	40 ± 1	35 ± 2	53 ± 1
5m	31 ± 1	61 ± 2	33 ± 1	37 ± 1	15 ± 1	10 ± 2	15 ± 3	45 ± 1	36 ± 1	82 ± 1	64 ± 1	47 ± 2	39 ± 1	70 ± 1
5n	10 ± 1	23 ± 1	14 ± 2	14 ± 1	30 ± 1	30 ± 2	21 ± 2	47 ± 2	41 ± 2	51 ± 1	52 ± 1	38 ± 1	25 ± 1	24 ± 1
5o	18 ± 2	23 ± 1	4 ± 3	75 ± 1	17 ± 1	13 ± 1	10 ± 2	42 ± 2	36 ± 1	68 ± 2	59 ± 1	42 ± 2	14 ± 1	26 ± 1
5p	9 ± 2	18 ± 3	7 ± 3	24 ± 2	18 ± 2	15 ± 1	31 ± 1	26 ± 2	29 ± 3	46 ± 2	45 ± 2	40 ± 1	16 ± 1	18 ± 2
5q	15 ± 2	24 ± 2	9 ± 1	16 ± 3	17 ± 2	11 ± 2	17 ± 3	36 ± 3	34 ± 2	52 ± 2	57 ± 2	37 ± 3	29 ± 1	13 ± 1
5r	25 ± 1	53 ± 1	23 ± 3	10 ± 1	15 ± 2	18 ± 1	10 ± 2	27 ± 1	44 ± 1	68 ± 3	70 ± 2	42 ± 1	25 ± 1	46 ± 2
5s	17 ± 1	42 ± 2	13 ± 1	8 ± 2	14 ± 2	9 ± 3	14 ± 2	31 ± 1	42 ± 2	50 ± 3	56 ± 2	42 ± 2	24 ± 3	45 ± 1
5t	12 ± 1	73 ± 1	23 ± 2	6 ± 1	12 ± 1	18 ± 1	28 ± 1	47 ± 2	56 ± 1	90 ± 1	91 ± 1	35 ± 1	39 ± 1	66 ± 2
5u	6 ± 1	30 ± 1	14 ± 2	24 ± 1	24 ± 1	5 ± 1	10 ± 1	37 ± 2	52 ± 1	65 ± 2	67 ± 3	60 ± 1	50 ± 1	30 ± 1
Carbendazim ^c	<50	100	100	<50	100	<50	100	<50	<50	<50	100	100	100	<50
Chlorothalonil ^c	73 ± 1	<50	86 ± 1	100	<50	100	100	100	73 ± 1	100	100	91 ± 1	91 ± 1	100

Open in a new tab

^a Average of three replicates. All results are expressed as the mean ± SD. ^b Abbreviations: AS—Alternaria solani; FG—Fusarium graminearum; PI—Phytophthora infestans; PC—Phytophthora capsici; SS—Sclerotinia sclerotiorum; BC—Botrytis cinerea; RS—Rhizoctonia solani.; FC—Fusarium oxysporum f. sp. cucumeris; CH—Cercospora arachidicola Hori; PP—Physalospora piricola; RC—Rhizoctonia cerealis; BM—Bipolaris maydis; WA—watermelon anthracnose; FM—Fusarium moniliforme. ^c commercial agricultural fungicides were used for comparison of antifungal activities.

3. Materials and Methods

Pymetrozine (Chemieliva Pharmaceutical Co., Ltd., Chongqing, China), carbendazim (Bailing Agrochemical Co., Ltd., Jiangyin, China), chlorothalonil (Bailing Agrochemical Co., Ltd., Beijing, China) and other reagents were used as received. All solvents were dried and purified using standard techniques. ¹H NMR and ¹³C NMR spectra were obtained at 400 MHz using a Bruker (Billerica, MA, USA) AV400 spectrometer in CDCl₃ or DMSO-d₆ solution with tetramethylsilane as the internal standard. Chemical shift values (δ) are given in parts per million. HRMS data were obtained on an FTICR-MS instrument (Ionspec 7.0 T, Agilent, Santa Clara, CA, USA). The melting points were determined using an X-4 binocular microscope melting-point apparatus and are uncorrected.

The biological assays for the foliar contact activity against bean aphid (A. craccivora), the larvicidal activities against mosquito larvae (C. pipiens pallens) and the stomach toxicity against cotton bollworm (H. armigera), oriental armyworm (M. separata) and corn borer (O. nubilalis) of compounds 3a–3w, 5a–5u and pymetrozine were conducted using the reported procedure [33,34,35]. The tests of fungicidal activities were carried out using the reported methods [36]. The testing process can also be found in the Supporting Information. The biological assays were repeated three times. The correcting mortality values were rounded to their nearest integers.

4. Conclusions

In summary, a series of novel triazone compounds containing aldehyde hydrazone or ketone hydrazone moieties were synthesized and evaluated for their insecticidal and fungicidal activities. Compounds 3t and 3w exhibited aphicidal activities comparable to pymetrozine. Compound 3u showed the highest larvicidal activity against C. pipiens pallens (40% at 0.1 mg/kg). In addition, most derivatives exhibited broad-spectrum fungicidal activities against 14 kinds of plant fungi at 50 mg/kg. A total of 20 compounds exhibited a more than 50% inhibition rate against F. graminearum at 50 mg/kg and 39 compounds exhibited a more than 50% inhibition rate against P. piricola. Triazone compounds containing hydrazone moieties could be further explored as candidate insecticides against aphids.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30020340/s1, File S1: the general preparation process of 3a–3w and 5a–5w, ¹H and ¹³C NMR data and spectra of 3a–3w and 5a–5w, detailed bioassay procedures for the anti-TMV activities and fungicidal activities.

molecules-30-00340-s001.zip^{(4.6MB, zip)}

Author Contributions

Synthesizing compounds and writing the manuscript, P.C.; synthesizing compounds and biological activity testing, Y.Y. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data will be made available on request.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding Statement

This research was funded by Fundamental Research Program of Shanxi Province, funding number 20210302123180 and 202303021221016, and the National Natural Science Foundation of China, funding number 22001190 and 21702144.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

1.Panini M., Anaclerio M., Puggioni V., Stagnati L., Nauen R., Mazzoni E. Presence and impact of allelic variations of two alternative s-kdr mutations, M918T and M918L, in the voltage-gated sodium channel of the green peach aphid Myzus persicae. Pest. Manag. Sci. 2015;71:878–884. doi: 10.1002/ps.3927. [DOI] [PubMed] [Google Scholar]
2.Malinga L.N., Laing M.D. Efficacy of three biopesticides against cotton pests under field condition in South Africa. Crop Prot. 2021;145:105578. doi: 10.1016/j.cropro.2021.105578. [DOI] [Google Scholar]
3.Torres J.B., Silva-Torres C.S.A., Oliveira J.V.D. Toxicity of pymetrozine and thiamethoxam to Aphelinus gossypii and Delphastus pusillus. Pesqui. Agropecu. Bras. 2003;38:459–466. doi: 10.1590/S0100-204X2003000400003. [DOI] [Google Scholar]
4.Kristinsson H. Pesticides. US4931439A. 1990 June 5;
5.Mulvihill M.J., Shaber S.H., Kelly M.J. Enhanced Propertied Pesticides. WO2001056358A2. 2001 August 9;
6.Sebastian R., Jurgen S., Shuji H. Insecticidal Triazinone Derivatives. WO2013079350A1. 2013 June 6;
7.Henry S., Haukur K. Imidazole Derivatives and Their Use as Agrochemical Agents. EP0604365A1. 1994 June 29;
8.Ali A.S., Wilkie J.S., Winzenberg K.N. Synthesis of some hydrazone derivatives structurally related to the insecticide pymetrozine. Aust. J. Chem. 1996;49:927–930. doi: 10.1071/CH9960927. [DOI] [Google Scholar]
9.Uehara M., Shimizu T., Fujioka S. Substituted Aminoquinzaolinone (Thione) Derivatives or Salts There of, Intermediates Ihereof, and Pest Controllers and a Method for Using the Same. EP0735035A1. 1996 March 28;
10.Osamus S., Masahiro U., Nobuyuki N. Process for Producing Substituted Aminoquinazolinone Derivative, Intermediate Therefore, and Pest Control Agent. WO2004099184A1. 2004 November 18;
11.Beriger E., Kristinsson H. Process for the Preparation of Aminotriazine Derivatives. US5324842A. 1994 June 28;
12.Henry S., Haukur K., Peter M., Josef E. Pyridine Derivatives as Pesticides. WO9518123. 1995 July 6;
13.Kristiansen O., Boger M., Kristinsson H., Maienfisch P. Pest Control Agents. US5179094A. 1993 January 2;
14.Wang B.Z., Ke S.Y., Kishore B., Xu X.Y., Zou Z.Y., Li Z. A facile synthesis of pyrimidone derivatives and single-crystal characterization of pymetrozine. Synth. Commun. 2012;42:2327–2336. doi: 10.1080/00397911.2011.551869. [DOI] [Google Scholar]
15.Uehara M., Shimizu T., Fujioka S., Kimura M., Seo A. Synthesis and insecticidal activity of 3-aminoquinazolinone derivatives. Pestic. Sci. 1999;55:359–362. doi: 10.1002/(SICI)1096-9063(199903)55:3<359::AID-PS906>3.0.CO;2-1. [DOI] [Google Scholar]
16.Nesterov A., Spalthoff C., Kandasamy R., Katana R., Rankl N.B., Andrés M., Jähde P., Dorsch J.A., Stam L.F., Braun F.J., et al. TRP channels in insect stretch receptors as insecticide targets. Neuron. 2015;86:665–671. doi: 10.1016/j.neuron.2015.04.001. [DOI] [PubMed] [Google Scholar]
17.Venkatachalam K., Montell C. TRP channels. Annu. Rev. Biochem. 2007;76:387–417. doi: 10.1146/annurev.biochem.75.103004.142819. [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Samanta A., Hughes T.E.T., Moiseenkova-Bell V.Y. Transient receptor potential (TRP) channels. Subcell. Biochem. 2018;87:141–165. doi: 10.1007/978-981-10-7757-9_6. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Xu Y.Y., Ren Y.N., Zhang J., Niu B., Liu M.R., Xu T.F., Zhang X., Shen J.H., Wang K., Cao Z.Y. Discovery of pyridazinone derivatives bearing tetrahydroimidazo [1,2-a] pyrazine scaffold as potent inhibitors of transient receptor potential canonical 5 to ameliorate hypertension-induced renal injury in rats. Eur. J. Med. Chem. 2024;275:116565. doi: 10.1016/j.ejmech.2024.116565. [DOI] [PubMed] [Google Scholar]
20.Yu M.L., Ledeboer M.W., Daniels M., Malojcic G., Tibbitts T.T., Gal M.C.L., Pan-Zhou X.R., Westerling-Bui A., Beconi M., Reilly J.F., et al. Discovery of a potent and selective TRPC5 inhibitor, efficacious in a focal segmental glomerulosclerosis model. ACS Med. Chem. Lett. 2019;10:1579–1585. doi: 10.1021/acsmedchemlett.9b00430. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Salgado V.L., Hayashi J.H. Metaflumizone is a novel sodium channel blocker insecticide. Vet. Parasitol. 2007;150:182–189. doi: 10.1016/j.vetpar.2007.08.032. [DOI] [PubMed] [Google Scholar]
22.Gorantla V., Gundla R., Jadav S.S., Anugu S.R., Chimakurthy J., Nidasanametla S.K., Korupolu R. Molecular hybrid design, synthesis and biological evaluation of N-phenyl sulfonamide linked N-acyl hydrazone derivatives functioning as COX-2 inhibitors: New anti-inflammatory, anti-oxidant and anti-bacterial agents. N. J. Chem. 2017;41:13516–13532. doi: 10.1039/C7NJ03332J. [DOI] [Google Scholar]
23.Zhang J.H., Wei C.L., Li S.Y., Hu D.Y., Song B.A. Discovery of novel bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties as potential antibacterial agents. Pestic. Biochem. Physiol. 2020;167:104605. doi: 10.1016/j.pestbp.2020.104605. [DOI] [PubMed] [Google Scholar]
24.Bi S.Y., Sun X.Y., Li X., Zhao R., Shao D. Depicting the binding of furazolidone/furacilin with DNA by multiple spectroscopies, voltammetric as well as molecular docking. Luminescence. 2020;35:493–502. doi: 10.1002/bio.3754. [DOI] [PubMed] [Google Scholar]
25.Xie J.L., Xu W.T., Song H.J., Liu Y.X., Zhang J.J., Wang Q.M. Synthesis and antiviral/fungicidal/insecticidal activities study of novel chiral indole diketopiperazine derivatives containing acylhydrazone moiety. J. Agric. Food Chem. 2020;68:5555–5571. doi: 10.1021/acs.jafc.0c00875. [DOI] [PubMed] [Google Scholar]
26.Cui P.P., Meng Y.N., Yang Y., Song H.J., Liu Y.X., Wang Q.M. Design, synthesis and biological activities of echinopsine derivatives containing acylhydrazone moiety. Sci. Rep. 2022;12:2935. doi: 10.1038/s41598-022-06775-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Fermini B., Jurkiewicz N.K., Jow B., Guinoso P.J., Baskin E.P., Lynch J.J., Salata J.J. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (Azimilide) on cardiac repolarization: Block of delayed rectifier potassium and L-type calcium currents. J. Cardiovasc. Pharmacol. 1995;26:259–271. doi: 10.1097/00005344-199508000-00012. [DOI] [PubMed] [Google Scholar]
28.Khrustalev D., Yedrissov A., Khrustaleva A., Mustafin M., Bekisheva K. Synthesis of anti-tuberculosis drugs in a microwave flow reactor. Mater. Today Proc. 2023;81:1186–1191. doi: 10.1016/j.matpr.2022.11.174. [DOI] [Google Scholar]
29.Walsh L., Reilly J.F., Cornwall C., Gaich G.A., Gipson D.S., Heerspink H.J.L., Johnson L., Trachtman H., Tuttle K.R., Farag Y.M.K., et al. Safety and efffcacy of GFB-887, a TRPC5 channel inhibitor, in patients with focal segmental glomerulosclerosis, treatment-resistant minimal change disease, or diabetic nephropathy: TRACTION-2 trial design. Kidney Int. Rep. 2021;6:2575–2584. doi: 10.1016/j.ekir.2021.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Villemure E., Terrett J.A., Larouche-Gauthier R., Déry M., Chen H.F., Reese R.M., Shields S.D., Chen J., Magnuson S., Volgraf M. A retrospective look at the impact of binding site environment on the optimization of TRPA1 antagonists. ACS Med. Chem. Lett. 2021;12:1230–1237. doi: 10.1021/acsmedchemlett.1c00305. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Yang Y., Liu Y.X., Song H.J., Li Y.Q., Wang Q.M. Design, synthesis, insecticidal activity, and structure-activity relationship (SAR): Studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels. Mol. Divers. 2016;20:919–932. doi: 10.1007/s11030-016-9687-6. [DOI] [PubMed] [Google Scholar]
32.Khodov I.A., Belov K.V., Pogonin A.E., Savenkova M.A., Gamov G.A. Spatial structure and conformations of hydrazones derived frompyridoxal 50-phosphate and 2-,3-pyridinecarbohydrazide in the light of NMR study and quantum chemical calculations. J. Mol. Liq. 2021;342:117372. doi: 10.1016/j.molliq.2021.117372. [DOI] [Google Scholar]
33.Abbott W.S. A method of computing the effectiveness of an insecticide. 1925. J. Am. Mosq. Control Assoc. 1987;3:302–303. [PubMed] [Google Scholar]
34.Song H.J., Liu Y.X., Xiong L.X., Li Y.Q., Yang N., Wang Q.M. Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing α-hydroxymethyl-N-benzyl carboxamide, α-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties. J. Agric. Food Chem. 2012;60:1470–1479. doi: 10.1021/jf204778v. [DOI] [PubMed] [Google Scholar]
35.Ma Q.Q., Liu Y.X., Zhang P.X., Li Y.Q., Xiong L.X., Wang Q.M. Design, synthesis, and biological evaluation of various α-substituted benzylpyrroles based on the structures of insecticidal chlorfenapyr and natural pyrrolomycins. J. Agric. Food Chem. 2014;62:6072–6081. doi: 10.1021/jf501377t. [DOI] [PubMed] [Google Scholar]
36.Lv P., Chen Y.L., Shi T.Z., Wu X.W., Li Q.X., Hua R.M. Synthesis and fungicidal activities of sanguinarine derivatives. Pestic. Biochem. Physiol. 2018;147:3–10. doi: 10.1016/j.pestbp.2017.06.009. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

molecules-30-00340-s001.zip^{(4.6MB, zip)}

Data Availability Statement

Data will be made available on request.

[B1-molecules-30-00340] 1.Panini M., Anaclerio M., Puggioni V., Stagnati L., Nauen R., Mazzoni E. Presence and impact of allelic variations of two alternative s-kdr mutations, M918T and M918L, in the voltage-gated sodium channel of the green peach aphid Myzus persicae. Pest. Manag. Sci. 2015;71:878–884. doi: 10.1002/ps.3927. [DOI] [PubMed] [Google Scholar]

[B2-molecules-30-00340] 2.Malinga L.N., Laing M.D. Efficacy of three biopesticides against cotton pests under field condition in South Africa. Crop Prot. 2021;145:105578. doi: 10.1016/j.cropro.2021.105578. [DOI] [Google Scholar]

[B3-molecules-30-00340] 3.Torres J.B., Silva-Torres C.S.A., Oliveira J.V.D. Toxicity of pymetrozine and thiamethoxam to Aphelinus gossypii and Delphastus pusillus. Pesqui. Agropecu. Bras. 2003;38:459–466. doi: 10.1590/S0100-204X2003000400003. [DOI] [Google Scholar]

[B4-molecules-30-00340] 4.Kristinsson H. Pesticides. US4931439A. 1990 June 5;

[B5-molecules-30-00340] 5.Mulvihill M.J., Shaber S.H., Kelly M.J. Enhanced Propertied Pesticides. WO2001056358A2. 2001 August 9;

[B6-molecules-30-00340] 6.Sebastian R., Jurgen S., Shuji H. Insecticidal Triazinone Derivatives. WO2013079350A1. 2013 June 6;

[B7-molecules-30-00340] 7.Henry S., Haukur K. Imidazole Derivatives and Their Use as Agrochemical Agents. EP0604365A1. 1994 June 29;

[B8-molecules-30-00340] 8.Ali A.S., Wilkie J.S., Winzenberg K.N. Synthesis of some hydrazone derivatives structurally related to the insecticide pymetrozine. Aust. J. Chem. 1996;49:927–930. doi: 10.1071/CH9960927. [DOI] [Google Scholar]

[B9-molecules-30-00340] 9.Uehara M., Shimizu T., Fujioka S. Substituted Aminoquinzaolinone (Thione) Derivatives or Salts There of, Intermediates Ihereof, and Pest Controllers and a Method for Using the Same. EP0735035A1. 1996 March 28;

[B10-molecules-30-00340] 10.Osamus S., Masahiro U., Nobuyuki N. Process for Producing Substituted Aminoquinazolinone Derivative, Intermediate Therefore, and Pest Control Agent. WO2004099184A1. 2004 November 18;

[B11-molecules-30-00340] 11.Beriger E., Kristinsson H. Process for the Preparation of Aminotriazine Derivatives. US5324842A. 1994 June 28;

[B12-molecules-30-00340] 12.Henry S., Haukur K., Peter M., Josef E. Pyridine Derivatives as Pesticides. WO9518123. 1995 July 6;

[B13-molecules-30-00340] 13.Kristiansen O., Boger M., Kristinsson H., Maienfisch P. Pest Control Agents. US5179094A. 1993 January 2;

[B14-molecules-30-00340] 14.Wang B.Z., Ke S.Y., Kishore B., Xu X.Y., Zou Z.Y., Li Z. A facile synthesis of pyrimidone derivatives and single-crystal characterization of pymetrozine. Synth. Commun. 2012;42:2327–2336. doi: 10.1080/00397911.2011.551869. [DOI] [Google Scholar]

[B15-molecules-30-00340] 15.Uehara M., Shimizu T., Fujioka S., Kimura M., Seo A. Synthesis and insecticidal activity of 3-aminoquinazolinone derivatives. Pestic. Sci. 1999;55:359–362. doi: 10.1002/(SICI)1096-9063(199903)55:3<359::AID-PS906>3.0.CO;2-1. [DOI] [Google Scholar]

[B16-molecules-30-00340] 16.Nesterov A., Spalthoff C., Kandasamy R., Katana R., Rankl N.B., Andrés M., Jähde P., Dorsch J.A., Stam L.F., Braun F.J., et al. TRP channels in insect stretch receptors as insecticide targets. Neuron. 2015;86:665–671. doi: 10.1016/j.neuron.2015.04.001. [DOI] [PubMed] [Google Scholar]

[B17-molecules-30-00340] 17.Venkatachalam K., Montell C. TRP channels. Annu. Rev. Biochem. 2007;76:387–417. doi: 10.1146/annurev.biochem.75.103004.142819. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B18-molecules-30-00340] 18.Samanta A., Hughes T.E.T., Moiseenkova-Bell V.Y. Transient receptor potential (TRP) channels. Subcell. Biochem. 2018;87:141–165. doi: 10.1007/978-981-10-7757-9_6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B19-molecules-30-00340] 19.Xu Y.Y., Ren Y.N., Zhang J., Niu B., Liu M.R., Xu T.F., Zhang X., Shen J.H., Wang K., Cao Z.Y. Discovery of pyridazinone derivatives bearing tetrahydroimidazo [1,2-a] pyrazine scaffold as potent inhibitors of transient receptor potential canonical 5 to ameliorate hypertension-induced renal injury in rats. Eur. J. Med. Chem. 2024;275:116565. doi: 10.1016/j.ejmech.2024.116565. [DOI] [PubMed] [Google Scholar]

[B20-molecules-30-00340] 20.Yu M.L., Ledeboer M.W., Daniels M., Malojcic G., Tibbitts T.T., Gal M.C.L., Pan-Zhou X.R., Westerling-Bui A., Beconi M., Reilly J.F., et al. Discovery of a potent and selective TRPC5 inhibitor, efficacious in a focal segmental glomerulosclerosis model. ACS Med. Chem. Lett. 2019;10:1579–1585. doi: 10.1021/acsmedchemlett.9b00430. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B21-molecules-30-00340] 21.Salgado V.L., Hayashi J.H. Metaflumizone is a novel sodium channel blocker insecticide. Vet. Parasitol. 2007;150:182–189. doi: 10.1016/j.vetpar.2007.08.032. [DOI] [PubMed] [Google Scholar]

[B22-molecules-30-00340] 22.Gorantla V., Gundla R., Jadav S.S., Anugu S.R., Chimakurthy J., Nidasanametla S.K., Korupolu R. Molecular hybrid design, synthesis and biological evaluation of N-phenyl sulfonamide linked N-acyl hydrazone derivatives functioning as COX-2 inhibitors: New anti-inflammatory, anti-oxidant and anti-bacterial agents. N. J. Chem. 2017;41:13516–13532. doi: 10.1039/C7NJ03332J. [DOI] [Google Scholar]

[B23-molecules-30-00340] 23.Zhang J.H., Wei C.L., Li S.Y., Hu D.Y., Song B.A. Discovery of novel bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties as potential antibacterial agents. Pestic. Biochem. Physiol. 2020;167:104605. doi: 10.1016/j.pestbp.2020.104605. [DOI] [PubMed] [Google Scholar]

[B24-molecules-30-00340] 24.Bi S.Y., Sun X.Y., Li X., Zhao R., Shao D. Depicting the binding of furazolidone/furacilin with DNA by multiple spectroscopies, voltammetric as well as molecular docking. Luminescence. 2020;35:493–502. doi: 10.1002/bio.3754. [DOI] [PubMed] [Google Scholar]

[B25-molecules-30-00340] 25.Xie J.L., Xu W.T., Song H.J., Liu Y.X., Zhang J.J., Wang Q.M. Synthesis and antiviral/fungicidal/insecticidal activities study of novel chiral indole diketopiperazine derivatives containing acylhydrazone moiety. J. Agric. Food Chem. 2020;68:5555–5571. doi: 10.1021/acs.jafc.0c00875. [DOI] [PubMed] [Google Scholar]

[B26-molecules-30-00340] 26.Cui P.P., Meng Y.N., Yang Y., Song H.J., Liu Y.X., Wang Q.M. Design, synthesis and biological activities of echinopsine derivatives containing acylhydrazone moiety. Sci. Rep. 2022;12:2935. doi: 10.1038/s41598-022-06775-7. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B27-molecules-30-00340] 27.Fermini B., Jurkiewicz N.K., Jow B., Guinoso P.J., Baskin E.P., Lynch J.J., Salata J.J. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (Azimilide) on cardiac repolarization: Block of delayed rectifier potassium and L-type calcium currents. J. Cardiovasc. Pharmacol. 1995;26:259–271. doi: 10.1097/00005344-199508000-00012. [DOI] [PubMed] [Google Scholar]

[B28-molecules-30-00340] 28.Khrustalev D., Yedrissov A., Khrustaleva A., Mustafin M., Bekisheva K. Synthesis of anti-tuberculosis drugs in a microwave flow reactor. Mater. Today Proc. 2023;81:1186–1191. doi: 10.1016/j.matpr.2022.11.174. [DOI] [Google Scholar]

[B29-molecules-30-00340] 29.Walsh L., Reilly J.F., Cornwall C., Gaich G.A., Gipson D.S., Heerspink H.J.L., Johnson L., Trachtman H., Tuttle K.R., Farag Y.M.K., et al. Safety and efffcacy of GFB-887, a TRPC5 channel inhibitor, in patients with focal segmental glomerulosclerosis, treatment-resistant minimal change disease, or diabetic nephropathy: TRACTION-2 trial design. Kidney Int. Rep. 2021;6:2575–2584. doi: 10.1016/j.ekir.2021.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B30-molecules-30-00340] 30.Villemure E., Terrett J.A., Larouche-Gauthier R., Déry M., Chen H.F., Reese R.M., Shields S.D., Chen J., Magnuson S., Volgraf M. A retrospective look at the impact of binding site environment on the optimization of TRPA1 antagonists. ACS Med. Chem. Lett. 2021;12:1230–1237. doi: 10.1021/acsmedchemlett.1c00305. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B31-molecules-30-00340] 31.Yang Y., Liu Y.X., Song H.J., Li Y.Q., Wang Q.M. Design, synthesis, insecticidal activity, and structure-activity relationship (SAR): Studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels. Mol. Divers. 2016;20:919–932. doi: 10.1007/s11030-016-9687-6. [DOI] [PubMed] [Google Scholar]

[B32-molecules-30-00340] 32.Khodov I.A., Belov K.V., Pogonin A.E., Savenkova M.A., Gamov G.A. Spatial structure and conformations of hydrazones derived frompyridoxal 50-phosphate and 2-,3-pyridinecarbohydrazide in the light of NMR study and quantum chemical calculations. J. Mol. Liq. 2021;342:117372. doi: 10.1016/j.molliq.2021.117372. [DOI] [Google Scholar]

[B33-molecules-30-00340] 33.Abbott W.S. A method of computing the effectiveness of an insecticide. 1925. J. Am. Mosq. Control Assoc. 1987;3:302–303. [PubMed] [Google Scholar]

[B34-molecules-30-00340] 34.Song H.J., Liu Y.X., Xiong L.X., Li Y.Q., Yang N., Wang Q.M. Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing α-hydroxymethyl-N-benzyl carboxamide, α-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties. J. Agric. Food Chem. 2012;60:1470–1479. doi: 10.1021/jf204778v. [DOI] [PubMed] [Google Scholar]

[B35-molecules-30-00340] 35.Ma Q.Q., Liu Y.X., Zhang P.X., Li Y.Q., Xiong L.X., Wang Q.M. Design, synthesis, and biological evaluation of various α-substituted benzylpyrroles based on the structures of insecticidal chlorfenapyr and natural pyrrolomycins. J. Agric. Food Chem. 2014;62:6072–6081. doi: 10.1021/jf501377t. [DOI] [PubMed] [Google Scholar]

[B36-molecules-30-00340] 36.Lv P., Chen Y.L., Shi T.Z., Wu X.W., Li Q.X., Hua R.M. Synthesis and fungicidal activities of sanguinarine derivatives. Pestic. Biochem. Physiol. 2018;147:3–10. doi: 10.1016/j.pestbp.2017.06.009. [DOI] [PubMed] [Google Scholar]

PERMALINK

Synthesis and Insecticidal/Fungicidal Activities of Triazone Derivatives Containing Acylhydrazone Moieties

Peipei Cui

Yan Yang

Roles

Abstract

1. Introduction

Figure 1.

Figure 2.

Figure 3.

2. Results and Discussions

2.1. General Synthesis

Scheme 1.

2.2. Biological Evaluation

2.2.1. Foliar Contact Activity Against Bean Aphid (A. craccivora)

Table 1.

Table 2.

2.2.2. Larvicidal Activities Against Mosquito (C. pipiens pallens), Cotton Bollworm (H. armigera), Oriental Armyworm (M. separata) and Corn Borer (O. nubilalis)

Table 3.

Table 4.

2.2.3. Fungicidal Activities

Table 5.

3. Materials and Methods

4. Conclusions

Supplementary Materials

Author Contributions

Institutional Review Board Statement

Informed Consent Statement

Data Availability Statement

Conflicts of Interest

Funding Statement

Footnotes

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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