Synthesis, in vitro and in-silico evaluation of amide derivatives as prospective antimicrobial and antileishmanial agents.

Abstract

This study focused on the synthesis, antimicrobial, and antileishmanial evaluation of seven amide derivatives (AL-1 to AL-7). The target compounds were synthesized from L-cysteine methyl ester and various substituted aromatic and aliphatic carboxylic acids. The final products were characterized using physical and spectro-analytical techniques (FT-IR, ¹H NMR). The derivatives were evaluated for their antimicrobial activity at various concentrations. Experimental studies revealed that compounds AL-5 and AL-6 were the most potent against Staphylococcus aureus and Escherichia coli, exhibiting 18 mm and 21 mm inhibition zones, respectively, at a concentration of 2000 µg/mL. Additionally, AL-5 and AL-6 showed significant activity against Candida albicans, with 20 mm and 23 mm inhibition zones, respectively, at a concentration of 1000 µg/mL. The compounds also exhibited moderate to good activity against Leishmania tropica. Compounds AL-2, AL-4, AL-5, and AL-6 demonstrated good activity, with IC₅₀ values of 0.68 ± 0.09, 0.68 ± 0.16, 0.66 ± 0.08, and 0.68 ± 0.12 µg/mL, respectively. Molecular docking, in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, and Density Functional Theory (DFT) studies were conducted on the most potent compounds (AL-5 and AL-6) to validate and support their experimental antimicrobial and antileishmanial potential.