title: Assessment of microtubule depolymerization property of flavonoids isolated from Tanacetum gracile in breast cancer cells by biochemical and molecular docking approach.
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.
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, U.P., India.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; School of Biosciences and Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, J&K 185131, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Amin
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Nayak
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, U.P., India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Bhatnagar
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, U.P., India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kacker
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Souneek
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Surinder
authors.initials: S
authors.lastname: Kitchlu
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Ram
authors.initials: R
authors.lastname: Vishwakarma
authors.affiliation: Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: agoswami@iiim.ac.in.
authors.forename: Anindya
authors.initials: A
authors.lastname: Goswami
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, U.P., India. Electronic address: sabarighosal@gmail.com.
authors.forename: Sabari
authors.initials: S
authors.lastname: Ghosal
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003078:Colchicine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D031203:Tanacetum / Q000737:chemistry*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; C054132:artemetin; C570121:chrysosplenetin; D003078:Colchicine
keywords: ADMET properties; Antitubulin agent; Flavonoids; Molecular docking; Reactive oxygen species; Tanacetum gracile