Synthesis, antioxidant and anticancer screenings of berberine–indole conjugates

Abstract

A variety of heterocyclic nitrogen cores in the form of indole moieties were linked to the natural isoquinoline alkaloid molecule berberine to achieve anticipated antioxidant and anticancer properties. An efficient synthetic pathway afforded final compounds 5a–j, which were tested in vitro for antioxidant potency using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical (ABTS) bioassays, and for anticancer activity using sulforhodamine B (SRB) assay against HeLa and Caski cancer cell lines. Moreover, the toxic nature of the resultant molecules was investigated using Madin–Darby canine kidney cells. The therapeutic indices of 5a–j were more appreciable against the Caski than HeLa cell line, in which compounds with electron-releasing alkyl or alkoxy functional group on indole entity as well as azaindole derivative performed well. In addition, these compounds were well endowed with antioxidant properties, in addition to the equal antioxidant effect of the compound with electron-withdrawing chlorine atom within indole entity. Adequate confirmation of the structure of the final analogues was achieved using Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), and mass spectroscopy and elemental (CHN) analysis.