Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects

摘要

A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe⁺³ reducing power in ABTS assay. The radical scavenging potential of the final derivatives >4a–>j was found excellent with IC50s, <13 μg/mL and < 8 μg/mL in DPPH and ABTS assay, respectively, whereas some analogues showed significant Fe⁺³ reducing power with absorption at around 2 nm in the FRAP assay. Anticancer effects of titled compounds were inspected against cervical cancer cell line Hela and Caski adapting SRB assay, in which analogues >4a–>j presented <6 μg/mL of IC50s, and >30 of therapeutic indices, thus exerting low cytotoxic values against Malin–Darby canine kidney (MDCK) cell lines at CC50s >125 μg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and ¹H NMR as well as elemental analyses.