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, Department of Food Science and Biotechnology, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Department of Bioresources and Food Sciences, College of Life and Environmental Sciences, Konkuk University, Seoul, Department of Bioresources and Food Sciences, College of Life and Environmental Sciences, Konkuk University, Seoul, Department of Bioresources and Food Sciences, College of Life and Environmental Sciences, Konkuk University, Seoul, Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology(KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Research Institute of Biotechnology & Medical Converged Science, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyenggi-do, Department of Biological and Environmental Science, College of Life Science and Biotechnology, Dongguk University-Ilsan, 32 Dongguk-ro, 410-820, Siksadong, Goyang-si, Gyenggi-do, Department of Food Science and Biotechnology, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820
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.
