Design, Synthesis and Evaluations of New 10-Triazolyl-1-methoxygenipin Analogues for Their Cytotoxicity to Cancer Cells

Abstract

© 2020 Wiley-VCH GmbH Genipin 1, derived from geniposide present in the fruit of Gardenia jasminoides Ellis has been reported to show diverse pharmacological activity. In this work, a new series of genipin-triazole analogues was designed and synthesized yielding high yields from naturally genipin and their cytotoxicity evaluated against six cancer cell lines. Twenty-seven analogues were obtained using a convenient four-step reaction methods. Six analogues showed higher cytotoxic activity than the original genipin and benzylether-triazolegenipin 5 j exhibited the strongest activity against P-388 and A-549 cancer cell lines with IC50 values of 2.54 and 4.53 μM. The structure-activity relationships (SARs) study indicated that the introduction of dibenzyl ether, substituted silyl and long chain aliphatic-triazoles at C-10 position of genipin were most effective in improving cytotoxicity. Molecular docking results provided the information for further modification of genipin scaffold for development as cytotoxic agent.