Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
No | R2″ | X | R4″ | R5″ | R6″ |
18 | H | N | H | H | H |
19 | H | CCl | H | H | H |
20 | H | CH | Cl | H | H |
21 | H | CH | H | H | H |
22 | H | CH | Ph | H | H |
23 | H | COCH3 | OCH3 | OCH3 | H |
2.2. Antiprotozoal Activity
3. Materials and Methods
3.1. Synthesis of 4-Ethoxycarbonylphenylphenyl Isothiocyanate 3
3.2. General Procedure for the Synthesis of Thiosemicarbazides 5–10
- Ethyl 4-(2-nicotinoylhydrazine-1-carbothioamido)benzoate (5). Solid beige, yield: 74%, mp: 200–202 °C. IR (cm−1): 3361 (NH), 3181 (CHarom), 2979 (CHali), 1710 (C=O), 1656 (C=O), 1601 (C=C), 1366 (NCS), 1273 (C-O). 1H NMR (100 MHz, DMSO d6) δ ppm: 1.35 (t, 3H, CH3, J = 7 Hz), 4.34 (q, 2H, CH2O, J = 7 Hz), 7.58 (dd, 1H, H5″, J = 7 Hz), 7.75 (d, 2H, H2′,6′, J = 8 Hz), 7.97 (d, 2H, H3′,5′, J = 8 Hz), 8.32 (d, 1H, H4″, J = 7 Hz), 8.79 (d, 1H, H6″, J = 5 Hz), 9.15 (s, 1H, H2″), 10.07 (brs, 2H, NH), 10.80 (brs, 1H, NH). 13C NMR (25.8 MHz, DMSO d6) δ ppm: 14.7, 61.1, 123.9, 124.8, 126.4, 128.7, 129.7, 136.0, 144.2, 149.4, 152.9, 165.2, 165.9, 181.8. Calcd for C16H16N4O3S: C, 55.80; H, 4.68; N, 16.27; S, 9.31. Found: C, 55.82; H, 4.67; N, 16.35; S, 9.43.
- Ethyl 4-[2-(3-chlorobenzoyl)hydrazine-1-carbothioamido]benzoate (6). White solid, yield: 62%, mp: 188–190 °C. IR (cm−1): 3317 (NH), 3160 (CHarom), 2981 (CHali), 1718 (C=O), 1634 (C=O), 1610 (C=C), 1352 (NCS), 1282 (C-O). 1H NMR (100 MHz, DMSO d6) δ ppm: 1.36 (t, 3H, CH3, J = 7 Hz), 4.38 (q, 2H, CH2O, J = 7 Hz), 7.50–8.05 (m, 8H, Ar), 9.95 (brs, 1H, NH), 10.06 (brs, 1H, NH), 10.72 (brs, 1H, NH). 13C NMR (25.8 MHz, DMSO d6) δ ppm: 14.7, 61.0, 124.6, 127.1, 128.2, 129.7, 130.8, 132.2, 133.6, 135.0, 144.3, 165.2, 181.8. Calcd for C17H16ClN3O3S: C, 54.04; H, 4.27; N, 11.12; S, 8.49. Found: C, 53.97, H, 4.32; N, 11.29; S, 8.73.
- Ethyl 4-[2-(4-chlorobenzoyl)hydrazine-1-carbothioamido]benzoate (7). White solid, yield: 59%, mp: 185–186 °C. IR (cm−1): 3300, 3211 (NH), 3174 (CHarom), 2975 (CHali), 1715 (C=O), 1612 (C=C), 1338 (NCS), 1277 (C-O). 1H NMR (100 MHz, DMSO d6) δ ppm: 1.28 (t, 3H, CH3, J = 7 Hz), 4.27 (q, 2H, CH2O, J = 7 Hz), 7.57 (d, 2H, H2′,6′, J = 8 Hz), 7.68 (brs, 2H, H3″,5″), 7.89 (d, 2H, H3′,5′, J = 8 Hz), 7.94 (d, 2H, H2″,6″, J = 8 Hz), 9.93 (brs, 1H, NH), 10.02 (brs, 1H, NH), 10.67 (brs, 1H, NH). 13C NMR(125 MHz, DMSO d6) δ ppm: 14.7, 61.1, 125.6, 126.6, 128.9, 129.6, 130.3, 131.7, 137.3, 144.2, 165.9, 180.2. Calcd for C17H16ClN3O3S: C, 54.04; H, 4.27; N, 11.12; S, 8.49. Found: C, 54.11, H, 4.29; N, 11.35; S, 8.61.
- Ethyl 4-(2-benzoylhydrazine-1-carbothioamido)benzoate (8). White solid, yield: 81%, mp: 176–178 °C. IR (cm−1): 3300 (NH), 3211 (NH), 3174 (CHarom), 2975 (CHali), 1698 (C=O), 1604 (C=C), 1338 (CNS), 1280 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 1.39 (t, 3H, CH3, J = 7 Hz), 4.36 (q, 2H, CH2O, J = 7 Hz), 7.53 (t, 1H, H4″, J = 8 Hz), 7.62–7.64 (m, 4H, Ar), 7.86 (d, 2H, H3′,5′, J = 8 Hz), 8.00–8.02 (m, 2H, Ar), 9.21 (brs, 1H, NH), 10.24 (brs, 1H, NH), 10.67 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.7, 61.0, 125.5, 126.6, 128.4, 128.8, 129.5, 132.4, 144.3, 165.9, 180.7. Calcd for C17H17N3O3S: C, 59.46; H, 4.99; N, 12.24; S, 9.34. Found: C, 59.53, H, 5.10; N, 12.41; S, 9.57.
- Ethyl 4-{2-[(1,1′-biphenyl)-4-carbonyl]hydrazine-1-carbothioamido}benzoate (9). White solid, yield: 78%, mp: 190–192 °C. IR (cm−1): 3307 (NH), 3254 (NH), 3152 (CHarom), 2981 (CHali), 1693 (C=O), 1659 (C=O), 1603 (C=C), 1284 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 1.25 (t, 3H, CH3, J = 7 Hz), 4.23 (q, 2H, CH2O, J = 7 Hz), 7.37 (t, 1H, 4′′′, J = 8 Hz), 7.45 (t, 2H, H3′′′, 5′′′, J = 8 Hz), 7.66 (d, 2H, H2′′′, 6′′′), 7.74 (d, 4H, H2″,6″,2′,6′, J = 8 Hz), 7.87 (d, 2H, Ar), 7.97 (d, 2H, H3′,5′, J = 8 Hz), 9.84 (brs, 1H, NH), 9.99 (brs, 1H, NH), 10.62 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.5, 61.4, 127.0, 128.8, 129.6, 139.3, 144.1, 166.2, 180.1. Calcd for C23H21N3O3S: C, 65.85; H, 5.05; N, 10.02; S, 7.64. Found: C, 65.91, H, 5.07; N, 9.87; S, 7.85.
- Ethyl 4-[2-(3,4,5-trimethoxybenzoyl)hydrazine-1-carbothioamido]benzoate (10). White solid, yield: 86%, mp: 196–198 °C. IR (cm−1): 3314 (NH), 3277 (NH), 3161 (CHarom), 2984 (CHali), 1728 (C=O), 1663 (C=C), 1610 (C=C), 1281 (C-O). 1H NMR (100 MHz, DMSO d6) δ ppm: 1.35 (t, 3H, CH3, J = 7 Hz), 3.77 (s, 3H, OCH3), 3.88 (s, 6H, OCH3), 4.33 (c, 2H, CH2O, J = 7 Hz), 7.33 (s, 2H, H2″,6″,), 7.74 (d, 2H, H2′,6′, J = 8 Hz), 7.95 (d, 2H, H3′,5′, J = 8 Hz), 10.02 (brs, 2H, NH), 10.54 (brs, 1H, NH). 13C NMR (25.8 MHz, DMSO d6) δ ppm: 14.7, 56.7, 60.8, 61.0, 106.2, 124.5, 127.9, 129.7, 144.3, 153.1, 165.8, 180.7. Calcd for C20H23N3O6S: C, 55.42; H, 5.35; N, 9.69; S, 7.40. Found: C, 55.29, H, 5.37; N, 9.93; S, 7.61.
3.3. General Procedure for the Synthesis of 4-[(1,3,4-Thiadiazol-2-yl)amino]benzoic Acid Derivatives 11–16
- 4-{[5-(Pyridin-3-yl)-1,3,4-thiadiazol-2-yl]amino}benzoic Acid (11). White solid, purification by recrystallization in ethanol–water, yield: 87%, mp: >300 °C. IR (cm−1): 3252 (NH), 3187 (NH), 3056 (CHarom), 2741 (OH), 1681 (C=O), 1601 (C=C), 1557 (C=N), 1418 (OH), 1268 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 7.55 (t, 1H, H5″, J = 5 Hz), 7.72 (d, 2H, H3′,5′, J = 8 Hz), 7.92 (d, 2H, H2′,6′, J = 8 Hz), 8.23 (d, 1H, H4″, J = 7 Hz), 8.65 (brs, 1H, H6″), 9.02 (brs, 1H, H2″), 10.99 (brs, 1H, COOH). 13C NMR (125 MHz, DMSO d6) δ ppm: 117.3, 124.9, 131.3, 133.6, 134.8, 139.1, 147.7, 151.5, 156.5, 161.1, 167.4. Calcd for C14H10N4O2S: C, 56.37; H, 3.38; N, 18.78; S, 10.75. Found: C, 56.31, H, 3.39; N, 18.95; S, 10.67.
- 4-{[5-(3-Chlorophenyl)-1,3,4-thiadiazol-2-yl]amino}benzoic Acid (12). Light yellow solid, purification by recrystallization in ethanol–water, yield: 75%, mp: 232–234 °C. IR (cm−1): 3255 (NH), 3187 (NH), 3056 (CHarom), 2981 (OH), 1674 (C=O), 1605 (C=C), 1553 (C=N), 1422 (OH), 1293 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 7.50–755 (m, 2H, H4″,6″), 7.75 (d, 2H, H3′,5′, J = 8 Hz), 7.79 (t, 1H, H5″, J = 8 Hz), 7.88 (s, 1H, H2″), 7.93 (d, 2H, H2′,6′, J = 8 Hz), 11.11 (brs, 1H, COOH). 13C NMR (125 MHz, DMSO d6) δ ppm: 117.3, 124.4, 126.2, 126.5, 130.6, 131.3, 131.7, 132.5, 134.4, 144.5, 157.6, 164.4, 167.4. Calcd for C15H10ClN3O2S: C, 54.30; H, 3.04; N, 12.67; S, 9.66. Found: C, 54.38, H, 2.98; N, 12.63; S, 9.78.
- 4-{[5-(4-Chlorophenyl)-1,3,4-thiadiazol-2-yl]amino}benzoic Acid (13). White solid, purification by recrystallization in ethanol–water, yield: 71%, mp: > 300 °C. IR (cm−1): 3248 (NH), 3187 (NH), 3174 (CHarom), 2920 (OH), 1640 (C=O), 1560 (C=N), 1480 (C=C), 1240 (C-O). 1H NMR (270 MHz, DMSO d6) δ ppm: 7.59 (d, 2H, Ar), 7.76 (d, 2H, H3′,5′, J = 8 Hz), 7.90 (d, 2H, Ar, J = 8 Hz), 7.97 (d, 2H, H2′,6′, J = 8 Hz), 10.98 (brs, 1H, NH), 12.70 (brs, 1H, COOH). 13C NMR (67.9 MHz, DMSO d6) δ ppm: 117.3, 124.4, 129.1, 129.5, 129.9, 131.4, 135.5, 144.6, 158.2, 164.2, 167.5. Calcd for C15H10ClN3O2S: C, 54.30; H, 3.04; N, 12.67; S, 9.66. Found: C, 54.27, H, 3.09; N, 12.81; S, 9.93.
- 4-[(5-Phenyl-1,3,4-thiadiazol-2-yl)amino]benzoic Acid (14). White crystalline solid, purification by recrystallization in ethanol–water, yield: 95%, mp: >300 °C. IR (cm−1): 3281 (NH), 3207 (NH), 3089 (CHarom), 2981 (OH), 1689 (C=O), 1611 (C=C), 1501 (OH), 1249 (C-O). 1H NMR (270 MHz, DMSO d6) δ ppm: 7.50–7.52 (m, 3H, Ar), 7.78 (d, 2H, H2′,6′, J = 8 Hz), 7.88–7.89 (m, 2H, Ar), 7.96 (d, 2H, H3′,5′, J = 8 Hz), 10.98 (brs, 1H, NH), 12.29 (brs, 1H, COOH). 13C NMR (67.9 MHz, DMSO d6) δ ppm: 117.3, 124.5, 127.5, 129.9, 130.7, 131.0, 131.4, 144.8, 159.2, 163.9, 167.5. Calcd for C15H11N3O2S: C, 60.59; H, 3.73; N, 14.13; S, 10.78. Found: C, 60.64, H, 3.73; N, 14.47; S, 10.87.
- 4-{[5-((1,1’-Biphenyl)-4-yl)-1,3,4-thiadiazol-2-yl]amino}benzoic Acid (15). White crystalline solid, purification by recrystallization in ethanol–water, yield: 84%, mp: >300 °C. IR (cm−1): 3281 (NH), 3207 (NH), 3089 (CHarom), 2981 (OH), 1689 (C=O), 1611 (C=C), 1501 (OH), 1249 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 7.68–7.72 (m, 5H, Ar), 7.75 (d, 2H, H3′,5′, J = 8 Hz), 7.82 (d, 2H, H3″,5″, J = 8 Hz), 7.93–7.95 (m, 4H, Ar), 10.90 (brs, 1H, COOH). 13C NMR (125 MHz, DMSO d6) δ ppm: 117.2, 126.5, 126.8, 127.9, 128.0, 129.7, 131.3, 139.4, 141.9, 148.5, 158.7, 163.9, 167.6. Calcd for C21H15N3O2S: C, 67.54; H, 4.05; N, 11.25; S, 8.59. Found: C, 67.43, H, 3.97; N, 11.43; S, 8.71.
- 4-{[5-(3,4,5-Trimethoxyphenyl)-1,3,4-thiadiazol-2-yl]amino}benzoic Acid (16). Brown solid, purification by recrystallization in ethanol–water, yield: 91%, mp: >300 °C. IR (cm−1): 3249 (NH), 3199 (NH), 3048 (CHarom), 2982 (OH), 1687 (C=O), 1601 (C=C), 1415 (OH), 1286 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 3.67 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 6.09–7.06 (m, 3H, Ar), 7.75 (d, 2H, H2′,6′, J = 8 Hz), 11.54 (brs, 1H, COOH). 13C NMR (125 MHz, DMSO d6) δ ppm: 56.5, 56.6, 60.9, 104.8, 117.1, 120.8, 123.8, 126.1, 131.2, 138.4, 144.8, 148.6, 153.7, 159.7, 163.7, 167.6. Calcd for C18H17N3O5S, C, 55.81; H, 4.42; N, 10.85; S, 8.28. Found: C, 55.78, H, 4.49; N, 11.09; S, 8.53.
3.4. General Procedure for the Synthesis of 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl 4-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]benzoate Derivatives 18–23
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-[(5-(pyridin-3-yl)-1,3,4-thiadiazol-2-yl]amino)benzoate (18). Beige solid, recrystallization from ethanol–water, yield: 55%, mp: 232–234 °C. IR (cm−1): 3273 (NH), 3199 (NH), 3057 (CHarom), 3000–2800 (CHali), 1715 (C=O), 1610 (C=C), 1491 (C=C), 1270 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.45 (s, 3H, CH3), 4.59 (t, 2H, CH2O, J = 5 Hz), 4.70 (t, 2H, CH2N, J = 5 Hz), 7.54 (m, 1H, H5”), 7.74 (d, 2H, H3′,5′, J = 9 Hz), 7.84 (d, 2H, H2′,6′, J = 9 Hz), 8.03 (s, 1H, H3), 8.25 (m, 1H, H4”), 8.67 (s, 1H, H2”), 9.05 (m, 1H, H6″), 11.06 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.4, 45.3, 62.9, 117.4, 122.4, 131.1, 133.6, 134.7, 145.1, 147.9, 151.6, 156.5, 164.3, 165.3. Calcd for C20H17N7O4S: C, 53.21; H, 3.80; N, 21.72; S, 7.10. Found: C, 53.32, H, 3.86; N, 21.84; S, 6.91.
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-{[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]amino}benzoate (19). White solid, recrystallization from ethanol–water, yield: 40%, mp: 202–204 °C. IR (cm−1): 3327 (NH), 3199 (NH), 3140–3070 (CHarom), 3000–2800 (CHali), 1690 (C=O), 1604 (C=C), 1496 (C=C), 1276 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.48 (s, 3H, CH3), 4.62 (t, 2H, CH2O, J = 5 Hz), 4.73 (t, 2H, CH2N, J = 5 Hz), 7.43 (m, 1H, H5”), 7.47 (d, 2H, H3′,5′, J = 8 Hz), 7.48 (m, 1H, H4″), 7.80 (d, 2H, H2′,6′, J = 8 Hz), 7.91 (m, 2H, H4, H6″), 7.95 (s, 1H, H2″), 11.01 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.7, 43.7, 62.3, 116.7, 120.1, 134.9, 129.0, 131.7, 132.9, 134.7, 134.8, 138.4, 144.0, 151.7, 152.7, 165.9, 174.1. Calcd for C21H17ClN6O4S: C, 52.02; H, 3.53; N, 17.33; S, 6.61. Found: C, 51.93, H, 3.61; N, 17.62; S, 6.87.
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-{[5-(4-chlorophenyl)-1,3,4-thiadiazol-yl]amino}benzoate (20). Beige solid, recrystallization from ethanol–water, yield: 54%, mp: 242–244 °C. IR (cm−1): 3273 (NH), 3199 (NH), 3114–3070 (CHarom), 3000–2800 (CHali), 1711 (C=O), 1613 (C=C), 1480 (C=C), 1271 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.45 (s, 3H, CH3), 4.58 (t, 2H, CH2O, J = 5 Hz), 4.69 (t, 2H, CH2N, J = 5 Hz), 7.54 (d, 2H, H3”,5”, J = 8,5 Hz), 7.72 (d, 2H, H3′,5′, J = 8.5 Hz), 7.80 (d, 2H, H2′,6′, J = 8.5 Hz), 7.85 (d, 2H, H2”,6”, J = 8.5 Hz), 8.02 (s, 1H, H4), 11.1 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.4, 45.3, 62.9, 117.3, 122.3, 128.9, 129.4, 129.8, 131.1, 133.6, 135.5, 139.1, 145.1, 151.9, 158.2, 163.9, 165.3. Calcd for C21H17ClN6O4S: C, 52.02; H, 3.53; N, 17.33; S, 6.61. Found: C, 52.17, H, 3.54; N, 17.29; S, 6.94.
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]benzoate (21). Beige solid, recrystallization from ethanol–water, yield: 60%, mp: 240–242 °C. IR (cm−1): 3277 (NH), 3200 (NH), 3120–3072 (CHarom), 2970 (CHali), 1702 (C=O), 1611 (C=C), 1492 (C=C), 1286 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.46 (s, 3H, CH3), 4.60 (t, 2H, CH2O, J = 5 Hz), 4.71 (t, 2H, CH2N, J = 5 Hz), 7.49–7.58 (m, 2H, Ar), 7.74 (d, 2H, H3′,5′, J = 8.5 Hz), 7.83 (d, 2H, H2′,6′, J = 8.5 Hz), 7.85–7.87 (m, 3H, Ar), 10.92 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.4, 45.3, 62.9, 117.3, 122.3, 127.4, 129.8, 129.9, 130.6, 130.9, 131.1, 133.6, 145.3, 159.4, 163.8, 165.4. Calcd for C21H18N6O4S: C, 55.99; H, 4.03; N, 18.66; S, 7.12. Found: C, 56.075, H, 4.01; N, 18.83; S, 7.37.
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-{[5-((1,1’-biphenyl)-4-yl)-1,3,4-thiadiazol-2-yl]amino}benzoate (22). Light yellow solid, recrystallization from ethanol–water, yield: 60%, mp: >300 °C. IR (cm−1): 3327 (NH), 3199 (NH), 3140 (CHarom), 3000–2800 (CHali), 1690 (C=O), 1604 (C=C), 1496 (C=C), 1276 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.49 (s, 3H, CH3), 4.61 (t, 2H, CH2O, J = 4.5 Hz), 4.74 (t, 2H, CH2N, J = 4.5 Hz), 7.70 (m, 5H, H Ar), 7.84 (d, 2H, H3′,5′, J = 8.5 Hz), 7.88 (2d, 4H, H Ar), 7.93 (d, 2H, H2’,6’, J = 8.5 Hz), 8.05 (s, 1H, H4), 11.04 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.3, 44.7, 62.4, 117.5, 121.8, 127.6, 127.9, 129.2, 129.9, 130.7, 132.9, 138.4, 140.6, 145.3, 151.4, 152.1, 163.4, 165.8. Calcd for C27H22N6O4S: C, 61.59; H, 4.21; N, 15.96; S, 6.09. Found: C, 61.75, H, 3.97; N, 15.83; S, 7.28.
- 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl-4-{[5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazol-2-yl]amino}benzoate (23). Yellow solid, recrystallization from ethanol–water, yield: 66%, mp: 252 °C. IR (cm−1): 3278 (NH), 3192 (NH), 3061 (CHarom), 3000–2820 (CHali), 1731 (C=O), 1604 (C=C), 1496 (C=C), 1267 (C-O). 1H NMR (500 MHz, DMSO d6) δ ppm: 2.48 (s, 3H, CH3), 3.70 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 4.59 (t, 2H, CH2O, J = 5 Hz), 4.70 (t, 2H, CH2N, J = 5 Hz), 7.12 (s, 2H, H6”), 7.39 (d, 2H, H3’,5’, J = 8 Hz), 7.74 (d, 2H, H2’,6’, J = 8 Hz), 8.11 (s, 1H, H4), 11.06 (brs, 1H, NH). 13C NMR (125 MHz, DMSO d6) δ ppm: 14.3, 45.2, 56.1, 60.8, 62.3, 105.3, 117.8, 122.1, 127.3, 130.7, 132.2, 138.4, 139.2, 144.8, 147.4, 152.7, 153.4, 164.5, 165.7. Calcd for C24H24N6O7S: C, 53.33; H, 4.48; N, 15.55; S, 5.93. Found: C, 53.37, H, 4.52; N, 15.71; S, 6.25.
3.5. Biology
3.5.1. Biological Material
3.5.2. In Vitro Evaluation of the Effect of Derivatives 17–22 on the Proliferation of Epimastigotes of Trypanosoma cruzi: MTT Test
3.5.3. In Vitro Evaluation of the Effect of Derivatives 17–22 on the Proliferation of Promastigotes of Leishmania donovani: MTT Test
3.5.4. Estimation of Half Maximal Inhibitory Concentration (IC50) of Derivatives 19, 20, and 21 on Epimastigotes of T. cruzi and Promastigotes of L. donovani: MTT Test
3.5.5. Host Cell Toxicity Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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T. cruzi | L. donovani | IC50 μM T. cruzi | IC50 μM L. donovani | |
---|---|---|---|---|
No | % Inhibition ± SD | |||
18 | 17.44 ± 14.42 | 10.08 ± 2.92 | nd | nd |
19 | 53.10 ± 3.68 | 31.77 ± 1.95 | 56.34 ± 6.83 | 59.72 ± 8.82 |
20 | 49.37 ± 4.45 | 40.38 ± 4.18 | 51.70 ± 6.59 | 54.48 ± 8.51 |
21 | 58.35 ± 2.05 | 71.42 ± 5.28 | 55.48 ± 7.20 | 10.07 ± 2.21 |
22 | 7.00 ± 2.28 | 12.95 ± 2.08 | nd | nd |
23 | 20.30 ± 6.73 | 12.74 ± 2.31 | nd | nd |
Mtz | 12.18 ± 5.30 | -- | 180.20 ± 18.9 | 50.31 ± 11.9 |
Bnz | 45.39 ± 6.21 | -- | nd | -- |
Nfx | 83.00 ± 1.60 | -- | 1.81 ± 0.45 | -- |
Aph | -- | 62.44 ± 6.60 | -- | 0.33 ± 0.02 |
No | CC50 (μM) | T. cruzi (SI) | L. donovani (SI) |
---|---|---|---|
19 | >500 | >8.87 | >8.37 |
20 | >500 | >9.67 | >9.17 |
21 | >500 | >9.01 | >49.65 |
Nfx | >90 | 48.65 | -- |
Aph | >250 | -- | 757.58 |
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Mijoba, A.; Parra-Giménez, N.; Fernandez-Moreira, E.; Ramírez, H.; Serrano, X.; Blanco, Z.; Espinosa, S.; Charris, J.E. Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani. Molecules 2024, 29, 4125. https://doi.org/10.3390/molecules29174125
Mijoba A, Parra-Giménez N, Fernandez-Moreira E, Ramírez H, Serrano X, Blanco Z, Espinosa S, Charris JE. Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani. Molecules. 2024; 29(17):4125. https://doi.org/10.3390/molecules29174125
Chicago/Turabian StyleMijoba, Ali, Nereida Parra-Giménez, Esteban Fernandez-Moreira, Hegira Ramírez, Xenón Serrano, Zuleima Blanco, Sandra Espinosa, and Jaime E. Charris. 2024. "Synthesis of Hybrid Molecules with Imidazole-1,3,4-thiadiazole Core and Evaluation of Biological Activity on Trypanosoma cruzi and Leishmania donovani" Molecules 29, no. 17: 4125. https://doi.org/10.3390/molecules29174125