Synthesis, <i>in vitro</i> and <i>in-silico</i> evaluation of amide derivatives as prospective antimicrobial and antileishmanial agents

This study focused on the synthesis, antimicrobial, and antileishmanial evaluation of seven amide derivatives (<b>AL-1</b> to <b>AL-7</b>). The target compounds were synthesized from <i>L-</i>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 <b>AL-5</b> and <b>AL-6</b> were the most potent against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, exhibiting 18 mm and 21 mm inhibition zones, respectively, at a concentration of 2000 µg/mL. Additionally, <b>AL-5</b> and <b>AL-6</b> showed significant activity against <i>Candida albicans</i>, 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 <i>Leishmania tropica</i>. Compounds <b>AL-2, AL-4, AL-5</b>, and <b>AL-6</b> 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, <i>in silico</i> Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis, and Density Functional Theory (DFT) studies were conducted on the most potent compounds (<b>AL-5</b> and <b>AL-6</b>) to validate and support their experimental antimicrobial and antileishmanial potential.