Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking

Abstract

The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (<b>8a-j</b>). The <i>in silico</i> antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the <i>in vivo</i> study, compound <b>8j</b> was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the <i>in vitro</i> antimicrobial activity, compounds <b>8a</b> and <b>8b</b> (MIC 1.2 × 10^-3 M and 1.1 × 10^-3 M) were most potent against <i>S. aureus</i>; compound <b>8a</b>, <b>8b</b>, and <b>8j</b> with MIC 6.0 × 10^-3 M, 5.7 × 10^-4 M, and 6.5 × 10^-4 M, respectively, were the most active against <i>B. subtilis</i>; compound <b>8b</b> (MIC 9.5 × 10^-4 M) was most active against <i>E.coli</i> while <b>8a</b>, <b>8b</b> and <b>8d</b> were the most active against <i>S. typhi</i>. Compounds <b>8c</b> and <b>8h</b> (MIC 1.3 × 10^-3 M) each were the most active against <i>C. albicans</i>, while compound <b>8b</b> (MIC 1.3 × 10^-4 M) was most active against <i>A. niger</i>.