Title:Synthesis and Evaluation of Antioxidant and Cytotoxicity of the N-Mannich Base of Berberine Bearing Benzothiazole Moieties
Volume: 17
Issue: 12
Author(s): Bhupendra M. Mistry, Han-Seung Shin, Young-Soo Keum, Muthuraman Pandurangan, Doo Hwan Kim, So Hyun Moon, Avinash A. Kadam, Surendra K. Shinde and Rahul V. Patel*
Affiliation:
- Department of Food Science and Biotechnology, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820,Korea
Keywords:
Berberine, benzothiazole, antioxidant, anticancer, N-Mannich base, synthesis.
Abstract: Background: Berberine, a quaternary ammonium salt from the protoberberine group of benzylisoquinoline
alkaloids has drawn high attention for its several biological potencies.
Objective: To furnish new rationalized derivatives based on berberine core which can deliver promising antioxidant
and cytotoxic activities.
Method: The N-Mannich base of an isoquinoline alkaloid, berberine, bearing substituted benzothiazole moieties
was obtained. Novel synthesized analogues were in vitro screened for antioxidant efficacy toward 2,2-diphenyl-
1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radicals and
in vitro cytotoxicity towards cervical cancer cell lines (HeLa and CaSki), an ovarian cancer cell line (SK-OV-3)
and human renal cancer cell line (Caki-2). Cytotoxicity of the compounds toward normal cell lines was examined
using the Madin-Darby canine kidney (MDCK) non-cancer cell line.
Results: Analogues bearing a methoxy functional group (5e), acid functionality (5c), and a cyano group (5m)
showed remarkable radical scavenging potential in DPPH and ABTS bioassays. Potent cytotoxicity exhibited by
berberine against the HeLa cell line was attributable to the presence of a 2-aminobenzothaizole moiety (5a) and
its 6-chloro congener (5g) on the berberine core, and the 6-cyano group (5m) on the benzothiazole ring revealed
strong sensitivity for the CaSki cell line, whereas subjected scaffolds demonstrated diminished activity against
the SK-OV-3 cell line. In addition, the compound with a 2-aminobenzothaizole moiety (5a), compound with
methoxy functional group (5e) and compound with cyano group appeared with the most significant cytotoxicity
effect in Caki-2 cell line. Their structures have been elucidated by FT-IR, 1H NMR, 13C NMR, and elemental
analyses (CHN) essential research.
Conclusion: N-Mannich bases of berberine were efficiently generated utilizing pharmacologically diverse substituted
2-aminobenzothiazole entities and final compounds were found remarkably active in antioxidant and
cytotoxic assay. Hence, such types of compounds can be further studied or rationalized in future drug discovery
studies.
