Click linker: efficient and high yielding synthesis of a new family of kojic acid congeners as cytotoxic agents

Nat Prod Res. 2021 Oct 31;1-7. doi: 10.1080/14786419.2021.1998897. Online ahead of print.

Abstract

Highly efficient methodology was developed for the construction of functionalized Kojic acid involving Click linker via 1,3-dipolar cycloaddition and their cytotoxicity against MCF-7, MIAPaCa-2 and DU145 mammalian cell lines were evaluated. Preliminary studies on structure-activity-relationship (SAR) revealed that substitution at C-2 of kojic acid as well as C-5 of 1,2,3-triazole motif played a major role in the activity profile. Kojic acid 1,2,3-triazole analogue 3 b containing an alkyl chain (n = 6) exhibited two fold potent activity than the parent compound, kojic acid against MCF-7 and MIA PaCa-2 cell lines. It induced apoptosis in these cell lines via ID1/PARP1 mediated pathway. The structures of the new analogues of kojic acid 1,2,3-triazole were confirmed by the detailed spectroscopic data analysis.

Keywords: 1,2,3-triazole; Aspergillus flavus; cytotoxicity; kojic acid.