. 2023 Feb 5;24(4):3144. doi: 10.3390/ijms24043144

Table 8.

Effect of tubercidin analogs with substitutions on C7 on Trypanosoma species and strains in vitro.

					T. congolense IL3000	T. congolense 6C3		T. vivax **	T.b.b. B48	T. evansi	T. equiperdum
Compound	C7	2′-OH	3′-OH	6-Position	EC₅₀ (µM)	EC₅₀ (µM)	RF ^†	EC₅₀ (µM)	EC₅₀ (µM)	EC₅₀ (µM)	EC₅₀ (µM)
Tubercidin	None	+	+	NH₂	3.16 ± 0.50	1.83 ± 0.39	0.58		4.30 ± 1.30
Cordycepin	None	+	−	NH₂	2.46 ± 0.42	2.16 ± 0.44	0.88	0.12 ± 0.02
FH7429_d *	None	+	−	NH₂	0.021 ± 0.001 *	0.019 ± 0.002 *	0.91	3.48 ± 0.09	0.25 ± 0.02	0.017 ± 0.002	0.0026 ± 0.0006
FH10677	None	−	+	NH₂	43.3 ± 14.5	10.9 ± 2.3	0.25	>64.0	38.0 ± 2.3	>100	17.4 ± 2.3
FH7429_u	Br	+	−	NH₂	0.00069 ± 0.00007	0.00049 ± 0.00009	0.71	0.018 ± 0.003	0.0048 ± 0.0005	0.00090 ± 0.00022	0.00051 ± 0.00007
FH8496	I	+	−	NH₂	0.0054 ± 0.0010	0.0030 ± 0.0002	0.56	0.056 ± 0.001	0.024 ± 0.002	0.0037 ± 0.0012	0.0015 ± 0.0005
FH8470 *	Cl	+	−	NH₂	0.0012 ± 0.0002	0.00066 ± 0.00003	0.53 ^a	0.096 ± 0.082	0.0068 ± 0.0009	0.0018 ± 0.0002	0.00057 ± 0.00008
FH8517	F	+	−	NH₂	0.0052 ± 0.0003	0.0031 ± 0.0003	0.60	0.50 ± 0.01	0.013 ± 0.002	0.0040 ± 0.0006	0.00052 ± 0.00011
FH10679	Br	−	+	NH₂	0.51 ± 0.09	0.31 ± 0.07	0.60	4.30 ± 0.90	1.04 ± 0.19	1.74 ± 0.53	0.067 ± 0.013
TH1003	Br	+	+	NH₂	0.79 ± 0.14	0.52 ± 0.031	0.66	0.74 ± 0.04	1.40 ± 0.09	0.48 ± 0.06	0.085 ± 0.026
FH3169	Cl	+	+	NH₂	0.86 ± 0.12	0.75 ± 0.14	0.87	0.053 ± 0.007	1.84 ± 0.33	0.62 ± 0.06	0.12 ± 0.018
FH3167	F	+	+	NH₂	0.45 ± 0.62	0.48 ± 0.10	1.06	0.038 ± 0.006	0.16 ± 0.03	0.18 ± 0.023	0.032 ± 0.007
FH6367	CF3	+	+	NH₂	1.80 ± 0.44	0.89 ± 0.17	0.50	0.82 ± 0.09	0.90 ± 0.13	0.68 ± 0.11	0.19 ± 0.03
FH9531	Cl	+	+	O-iPr	4.04 ± 0.36 *	3.23 ± 0.36 *	0.80	0.12 ± 0.01
FH8505	ethynyl	+	−	NH₂	0.017 ± 0.002	0.0080 ± 0.002	0.46 ^a	0.16 ± 0.01	0.031 ± 0.004	0.0078 ± 0.0020	0.0026 ± 0.0008
FH10659	vinyl	+	−	NH₂	0.056 ± 0.004	0.040 ± 0.003	0.70	1.57 ± 0.43		0.038 ± 0.0015	0.011 ± 0.001
TH1008 *	Pyridin-2-yl	+	+	NH₂	0.17 ± 0.05	0.056 ± 0.013	0.33	12.9 ± 4.4	0.39 ± 0.03	0.040 ± 0.005	0.061 ± 0.005
Diminazene					0.23 ± 0.04	1.32 ± 0.43	5.7 ^a		0.34 ± 0.13
Pentamidine					0.55 ± 0.11	0.44 ± 0.15	0.79		0.34 ± 0.06

All EC₅₀ values were obtained by Alamar Blue (resazurin) assays and are shown as averages in nM (±SEM) of at least 3 independent determinations. EC₅₀ values were obtained using the resazurin-based assay in 96-well plates, with doubling dilutions over 1 or 2 rows (11 or 23 dilutions) as necessary to obtain a full EC₅₀. When inhibition was less than 50% at 100 µM the value is listed as >100. 6C3 = diminazene resistant; B48 = multidrug-resistant T. brucei strain. ^† RF = resistance factor, in comparison to wild-type or parental strain, being EC₅₀ (test strain)/EC₅₀(control strain). ^a p ≤ 0.05 by unpaired Student’s t-test. * EC₅₀ obtained from Hulpia et al. [38]. ** EC₅₀ obtained from Mabille et al. [69], added for comparison only.