Azide–Alkyne Cycloaddition En Route to 1<i>H</i>-1,2,3-Triazole-Tethered Isatin–Ferrocene, Ferrocenylmethoxy–Isatin, and Isatin–Ferrocenylchalcone Conjugates: Synthesis and Antiproliferative Evaluation

Abstract

Diverse series of isatin-ferrocene conjugates were synthesized via Cu-promoted azide-alkyne cycloaddition reaction with an aim of probing their antiproliferative structure-activity relationship against MCF-7 (estrogen receptor positive) and MDA-MB-231 (triple negative) cell lines. Among the synthesized conjugates, isatin-ferrocenes proved to be more potent against MCF-7, whereas ferrocenylmethoxy-isatins exhibited activity against MDA-MB-231 cell lines. However, the introduction of chalcone moiety among these hybrids resulted in the complete loss of activity against the tested cell lines, as evident by isatin-ferrocenylchalcones. The conjugates <b>5a</b> and <b>9c</b> proved to be the most potent among the series against MCF-7 and MDA-MB-213 cell lines, exhibiting IC₅₀ values of 31.62 and 20.26 μM, respectively.