Issue 6, 2024

Synthesis and anticancer evaluation of [d-Ala]-nocardiotide A

Abstract

Cancer is currently one of the biggest causes of death in the world. Like some microorganisms, cancer cells also develop resistance to various chemotherapy drugs and are termed multidrug resistant (MDR). In this regard, there is a need to develop new alternative anticancer agents. Anticancer peptides (ACPs) with high selectivity and high cell penetration ability are a promising candidate, as well as they are easy to modify. A cyclohexapeptide called nocardiotide A was isolated from the marine sponge Callyspongia sp., which is cytotoxic towards several cancer cells such as MM, 1S, HeLa, and CT26 cells. Previously, nocardiotide A was synthesized with a very low yield owing to its challenging cyclization process. In this study, we synthesized [D-Ala]-nocardiotide A as a derivative of nocardiotide A using a combination of solid phase peptide synthesis (SPPS) and liquid phase peptide synthesis (LPPS). The synthesis was carried out by selecting a D-alanine residue at the C-terminus to give a desired cyclic peptide product with a yield of 31% after purification. The purified [D-Ala]-nocardiotide A was characterized using HR-ToF MS and 1H and 13C-NMR spectroscopy to validate the desired product. The anticancer activity of the peptide was determined against HeLa cancer cell lines with an IC50 value of 52 ÎĽM compared to the parent nocardiotide A with an IC50 value of 59 ÎĽM. In the future, we aim to mutate various L-amino acids in nocardiotide A to D-amino acids to prepare nocardiotide A derivatives with a higher activity to kill cancer cells with higher membrane permeation. In addition, the mechanism of action of nocardiotide A and its derivatives will be evaluated.

Graphical abstract: Synthesis and anticancer evaluation of [d-Ala]-nocardiotide A

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Article information

Article type
Paper
Submitted
02 Jan 2024
Accepted
16 Jan 2024
First published
30 Jan 2024
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2024,14, 4097-4104

Synthesis and anticancer evaluation of [D-Ala]-nocardiotide A

R. Maharani, M. I. Muhajir, J. M. Dirgantara, A. Hardianto, T. Mayanti, D. Harneti, Nurlelasari, K. Farabi, A. T. Hidayat, U. Supratman and T. Siahaan, RSC Adv., 2024, 14, 4097 DOI: 10.1039/D4RA00025K

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