Table 1.
Synthesis and reaction conditions related to therapeutic potential of p-aminobenzoic acid derivatives.
| Derivatives of PABA | Synthetic Conditions | Characterization Techniques |
Physical Properties | Biological Activity | IC50 (µM) | Reference |
|---|---|---|---|---|---|---|
| Nonyl 4-nonylamino)benzoate | PABA, alkylating agent, K2CO3, acetone, 5–6 h | EIMS, FTIR, 1H-NMR, and 13C NMR | Amorphous white solid | Cytotoxicity activity against the NCI-H460 cell line | NCI-H460: 15.59 | [112] |
| 4-((5,6,7,8-tetrahydrobenzo [4,5]thieno [2,3-d]pyrimidin-4-yl)amino)benzoic acid | 4-chloro-6,7,8,9-tetrahydro-5H-indeno [2,1-d]pyrimidine, PABA, ethanol, reflux, 4 h | EIMS, FTIR, 1H NMR, and 13C NMR | Yellow crystal, Yield: 88%, m.p: 280–282 °C |
Cell lines: EGFRT790M and HER2 kinases and 4 cancer cell lines of HCT-116, HepG2, A431, and MCF-7 | HepG2: 67.72 ± 3.70 HCT-116: 62.57 ± 3.30 MCF-7: 75.75 ± 3.40 |
[113] |
| N-(tert-butyl)-4-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamido)benzamide | N-(tert-butyl)-4-(2-chloroacetamido) benzamide, potassium salt of 3-methylquinoxalin-2(1H)-one, DMF, KI, heating 3 h | 1H NMR, 13C NMR, and FTIR | Dark green crystal, Yield: 80%, m.p: 230–232 °C |
Cytotoxicity against HepG2 and MCF-7 cell lines | MCF-7: 7.7, HepG2: 4.5 | [114] |
| 2-(4-((2-Oxoindolin-3-ylidene)amino)benzoyl)-N-phenylhydrazinecarbothioamide | 4-((5-Substituted-2-oxoindolin-3-ylidene)amino)benzohydrazide, Isothiocyanatobenzene, EtOH, Reflux, 8 h. |
EIMS, FTIR, 1H NMR, and 13C NMR | Yellow powder, Yield: 93%, m.p: 211–213 °C |
Cytotoxic activity against HepG2 cell line, MCF-7 cell line, VEGFR-2 kinase inhibitory assay |
MCF-7: 0.74–4.62 HepG2: 1.13–8.81 VEGFR-2: 0.078 | [19] |
| ((E)-N-(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide) | 2,2,2-Trifluoro-N-(4-(hydrazinecarbonyl)phenyl)acetamide, N-(3-acetylphenyl)nicotinamide, 6 h and absolute ethanol | EIMS, FTIR, 1H NMR, and 13C NMR | Off-white crystals Yield: 80%, m.p: 246–248 °C |
Cytotoxic properties against VEGFR-2, MCF-7 cell lines, and HepG2 | VEGFR-2: 65 nM HepG2: 21.00, MCF-7: 26.10 | [115] |
| 3α-O-(4-acrylamidebenzoyl)-4β-hydroxy-5,7α,6β(H)-guaia-1(10),11(13)-dien-12,6-olide | 3α,4β-dihydroxy-5,7α,6β(H)-guaia-1(10),11(13)-dien12,6-olide, 4-acrylamidobenzoic acid, DCC, DMAP, CH2Cl2, | 1H NMR, 13C NMR, and HRESIMS | White powder, Yield: 56%, m.p: 120–122 °C |
Cytotoxicity against Huh7 and HepG2 cell lines | HepG2: 7.9 ± 0.3 Huh: 78.5 ± 0.2 |
[116] |
| Ag-PABA complex | PABA, KOH, AgNO3, 1 h | XRD, mass spectrometry, 1H NMR, 2D NMR, and 13C NMR | White solid | In vitro antibacterial activity | MIC value (µM) S. aureus ATCC 25923: 88.5 B. cereus ATCC 14579: 88.5 E. coli: 44.0 |
[117] |
| 4-[1-(1,3-Dihydro-benzoimida-zol-2-ylideneamino)-oct-2-ynylideneamino]-benzoic acid | Oct-2-ynoic acid (1,3-dihydrobenzoimidazole-2-ylidene)amide, aniline derivatives, warm ethanoic solution and refluxing for 4 h | UV–Vis absorption, FTIR, 13C NMR, 1H NMR, and C, H, N elemental analysis | White powder, Yield: 73%, m.p. 175.2 °C |
Anti-plasmodial activity |
Plasmodium Falciparum 3D7: 28.31 µg/mL |
[118] |
| Peanut skin extract-azo-compounds and complexes with iron | NaNO2, HCl, ice, peanut skin extract, FeCl2, methanol, 65 °C, reflux 3 h |
SEM-EDS analysis, FTIR, and UV-visible spectroscopy | Deep orange, Yield: 56.81%, m.p: > 300 °C |
Antimicrobial activity against Staphylococcus aureus and Escherichia coli | Inhibition zone (mm) E. Coli:10.0 ± 0.33 S. aureus: 6.0 ± 1.52 |
[119] |
| 4-(1H-Indole-2-carboxamido)benzoic acid | Dry pyridine, CHCl3,1H-Indole-2-carbonyl chloride | NMR, IR spectroscopy, HRMS, and elemental analysis techniques | Yield: 86%, m.p: 256–258 °C |
Antifungal and antibacterial activity | Inhibition zone (mm) C. albicans DSMZ 11949: 9–14 |
[120] |
| Methyl (S)-2-(4-(4-methylphenylsulfonamido)benzamido)propanoate | Amino acid methyl ester hydrochloride, 4-(4-methylphenylsulfonamido)benzoic acid, DCC, HOBt, DIPEA, THF, | 1H NMR, 13C NMR, and HRMS | Yield: 92%, m.p. 203.1–203.9 °C |
In vitro PPRE-activated activity | PPRE-activated activity: 87% | [27] |
| 2-((4-(N-(4-Carboxyphenyl)sulfamoyl)phenyl)carbamoyl)benzoic acid | 2-((4-(N-(4-(Ethoxycarbonyl)phenyl)sulfamoyl)phenyl)carbamoyl)benzoic acid, NaOH, EtOH, 80 °C, 18 h | 13C NMR, 1H NMR, and HRMS (ESI) | White powder, Yield: 82%, m.p. 203–205 °C | Antiviral activity against Nancy, coxsackievirus B3. CVB3 | CVB3: 4.22 Nancy: 4.29 |
[121] |
| N,N’-(1,2-phenylene) bis(4-aminobenzamide) and its complexes | ethyl 4-aminobenzoate, 1,2-Benzene diamine, reflux 3 h, MCl2, reflux |
UV-Vis, FTIR, 1H NMR, and elemental analyses | Pale green, Yield: 45%, m.p: 230 °C |
Antibacterial activity against S. aureus and E. coli | Diameters of antibacterial activity S. aureus: 25 mm E. coli: 28 mm |
[122] |
| N-(2-(1-benzylpiperidin-4-yl)ethyl)-4-((3,5-dimethoxybenzyl)amino)benzamide |
4-Amino-N-(2-(1-benzylpiperidin-4-yl)ethyl)benzamide, benzyl halide ACN, 80 °C, 6 h, |
13C NMR, 1H NMR, and HRMS (ESI) | Yellow solid, Yield: 80%, m.p: 118–120 °C |
Activity against ChE enzymes | AChE: 0.61, BchE: 2.04 | [123] |
| N-(4-{[(2E)-2-(4-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside)-3-metoxybenzylidene)hydrazino]carbonyl}phenyl)benzamide | galactoside, N-(4-(hydrazinecarbonyl)phenyl)benzamide, ethyl alcohol, r.t, HCl, stirring for 24 h |
13C NMR, 1H NMR HRMS (ESI), and FTIR |
White crystals, Yield: 84%, m.p: 137–138 °C |
Antifungal activity | C. glabrata: 695.2 | [124] |
| 4-(4-(1-(2-Isonicotinoylhydrazono)ethyl)phenylsulfonamido)benzoic acid | Acetylbenzenesulfonamide derivatives, hydrazide derivatives, methanol, 2 h, glacial acetic acid | UV, IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis | White solid, Yield: 41% m.p: 288–290 °C |
AChE activity | AChE: 11.12 ± 0.74 | [125] |
| N-(3-(Hydroxycarbamoyl)phenyl)-3,5,6-Trimethylpyrazine-2-Carboxamide | 4-(3,5,6-trimethylpyrazine-2-carboxamido)benzoic acid, NH2OH, | 1H NMR | Yield: 52% m.p: >250 °C |
Antiproliferative activities against two HDAC-expressing cancer cell lines: HT-29 and SH-SY5Y | HT-29 cells: 1.96 | [126] |
| Cu(PABA)2(H2O)2 complex | Metal and ligand 1:2 molar ratio (M:L), 30 min, pH value at 5.6, r.t | FTIR and UV-vis spectroscopy | Dark green product | Antimicrobial activity | Inhibition zone (mm) Enterococcus faecalis: 16 S. aureus: 11 |
[14] |
| 4-(2-(4-(1H-Benzimidazol-2-yl)phenyl)hydrazono)-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one | Ethyl 2-(2-(4-(1H-benzimidazol-2-yl)phenyl) hydrazono)-3-oxobutanoate, hydrazine hydrochloride, ethanol, refluxed for 12 h | EIMS, FTIR, 1H NMR, and 13C NMR | Yield: 82%, m.p: 197–200 °C | Antimicrobial activity | MIC (µg/mL) S. aureus: 7.81 S. epidermidis: 1.95 E. coli: 7.81 |
[127] |