Assessment of microtubule depolymerization property of flavonoids isolated from Tanacetum gracile in breast cancer cells by biochemical and molecular docking approach. (5th September 2015)

• Record Type: Journal Article
• Authors: Sinha, Sadhna; Amin, Hina; Nayak, Debasis; Bhatnagar, Manisha; Kacker, Puneet; Chakraborty, Souneek; Kitchlu, Surinder; Vishwakarma, Ram; Goswami, Anindya; Ghosal, Sabari
• Is Part Of: Chemico-biological interactions. Volume 239(2015)
• Page Start: 1
• Page End: 11
• Publication Date: 2015-09-05
• Subjects: Flavonoids -- Tanacetum gracile -- Antitubulin agent -- Reactive oxygen species -- Molecular docking -- ADMET properties; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2015.06.034
• Languages: English
• ISSNs: 0009-2797

Abstract

Graphical abstract: Highlights: Isolation and characterization of cytotoxic flavone analogues from Tanacetum gracile . Microtubule depolymerization by activating mitotic spindle checkpoint. Molecular docking to understand probable inhibition mechanism. Abstract: The chemical investigation of the bioactive nonpolar fractions of Tanacetum gracile afforded two flavonoid analogues namely, 5-hydroxy-3, 6, 7, 3′, 4′-pentamethoxyflavone (1 ) and 5, 4′-dihydroxy-3, 6, 7, 3′, 4′-tetramethoxyflavone (2 ) which were identical to the previously reported artemetin and chrysosplenetin respectively. The structure of the compounds was elucidated on the basis of spectroscopic evidences and they showed significant cytotoxic activity against human breast cancer cells (MCF-7 and T47D). Mechanism based study showed that the compounds modulated microtubule depolymerization by activating mitotic spindle checkpoint. Molecular docking at the colchicine binding pocket revealed that the compounds bind at α–β interfacial site of tubulin, correlating binding interactions with probable inhibition mechanism. The study reveals important observations to generate improved flavonoids that leads to cell apoptosis. The compounds were also evaluated for absorption, metabolism and toxicity by online webserver admetSAR. The significant microtubule disassembling property and less toxicity paves way for consideration of the compounds as chemopreventive agents.