Synthesis In-Vitro Antibacterial Antifungal and Molecular Modeling of Potent Anti-Microbial Agents with a Combined Pyrazole and Thiophene Pharmacophore

摘要

Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (>2) and there derivatives >3a–>c, >4, >6a–>c and >9a–>f were synthesized. The structure of compound >2 was deduced by ¹H-NMR, ¹³C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P21/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, β = 101.131(6)°, V = 1468.7(4) ų, and Z = 4. Compounds >2, >3a–>c, >4, >5a–>c and >9a–>f were subjected into in vitro antimicrobial activity tests. Compounds >3a and >3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound >3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds >4 and >9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds.