Synthesis of piperazine based N-Mannich bases of berberine and their antioxidant and anticancer evaluations

摘要

Isoquinoline alkaloids possess versatile biological activities. Hence, in the current research an effort has been made to improve structurally important part of isoquinoline alkaloid berberine because it is recognized as the marking compound for the crude drugs. Synthesis of rationalized berberine has been performed via substituting various piperazine moieties bearing disubstituted electron withdrawing and electron donating groups to the berberine core via Mannich reaction. Intended scaffolds were inspected for their in vitro antioxidant potential using different bioassays, FRAP, DPPH and ABTS as well as anticancer efficacies against cervical cancer cell lines HeLa, CaSki adapting SRB assay. Also, an inspection of the cytotoxic nature of titled analogues has been carried out towards Madin-Darby canine kidney (MDCK) cell lines. Radical scavenging potential of the final derivatives 4a-i was found to be excellent with IC50s, <20 and <12 mu g/mL in DPPH and ABTS assay, respectively, whereas some dichlorophenyl piperazine analogues revealed important Fe3+ decreasing power with absorption at around 2 nm in FRAP assay. Moreover, compounds 4a-i appeared with significant inhibitors of the cervical cancer cell lines HeLa and CaSki with IC50s ranging 4.346-6.321 and 3.408-6.081 mu g/mL, with low level of cytotoxic values and higher therapeutic indices ranging 20.42-42.45 and 21.23-43.25, respectively. Therefore, from the bioassay results it can be mentioned that these analogues are effective double agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells. The correct structure of the final compounds was adequately confirmed on the basis of FT-IR, H-1 NMR and mass spectroscopy data as well as elemental analyses.