Design and synthesis of acyldepsipeptide-1 analogues: antibacterial activity and cytotoxicity screening

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Date

2023

Journal Title

Journal ISSN

Volume Title

Publisher

Arabian Journal of Chemistry

Abstract

Acyldepsipeptides (ADEPs) are receiving more attention as prospective antimicrobial agents due to their unique mode of action and chemical properties. However, their therapeutic potential is limited by their poor pharmacokinetic properties. Chemical modifications have been successful in improving the biocompatibility and bioavailability of ADEPs. In the current study, ADEP1 was modified by introducing a disulphide linkage, replacement of the octa-2,4,6-trienoic acid (OTEA) with either adamantane (Ada) or palmitic acid (Pal), and lastly, comparing the use of D versus L amino acids. The antibacterial effects of the ADEP1 analogues were investigated in Gram-positive and Gram-negative strains using agar well diffusion and microdilution assays. Cytotoxicity was evaluated in human embryonic kidney (HEK)-293 and colon cancer (Caco-2) cells by the MTS assay. Using solid phase peptide synthesis (SPPS), the percentage yield of the synthetic peptides was increased to > 37% with > 96% purity.

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Keywords

Acyldepsipeptides, Adamantane, Antimicrobial peptides, Caseinolytic protease, Palmitic acid

Citation

Cobongela, S.Z., Makatini, M.M., Njengele-Tetyana, Z., Sikhwivhilu, L.M. and Sibuyi, N.R., 2023. Design and synthesis of Acyldepsipeptide1 analogues: Antibacterial activity and cytotoxicity screening. Arabian Journal of Chemistry, p.105000.