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

James A Ezugwu; Uchechukwu C Okoro; Mercy A Ezeokonkwo; China R Bhimapaka; Sunday N Okafor; David I Ugwu; Ogechi C Ekoh; Solomon I Attah

doi:10.3389/fchem.2020.583926

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

Front Chem. 2020 Nov 24:8:583926. doi: 10.3389/fchem.2020.583926. eCollection 2020.

Authors

James A Ezugwu^{1

2}, Uchechukwu C Okoro¹, Mercy A Ezeokonkwo¹, China R Bhimapaka², Sunday N Okafor³, David I Ugwu¹, Ogechi C Ekoh⁴, Solomon I Attah¹

Affiliations

¹ Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria.
² Organic Synthesis and Process Chemistry, Council for Scientific and Industrial Research-India Institute of Chemical Technology, Hyderabad, India.
³ Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Nigeria.
⁴ Department of Industrial Chemistry, Evangel University Akaeze, Enugu, Nigeria.

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 (8a-j). The in silico 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 in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10^-3 M and 1.1 × 10^-3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10^-3 M, 5.7 × 10^-4 M, and 6.5 × 10^-4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10^-4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10^-3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10^-4 M) was most active against A. niger.

Keywords: Leu-Val dipeptide; antimalarial; antimicrobial; benzenesulfonamide; in silico studies.