title: Identification of gallic acid based glycoconjugates as a novel tubulin polymerization inhibitors.
abstract: A novel class of gallic acid based glycoconjugates were designed and synthesized as potential anticancer agents. Among all the compounds screened, compound 2a showed potent anticancer activity against breast cancer cells. The latter resulted in tubulin polymerization inhibition and induced G2/M cell cycle arrest, generation of reactive oxygen species, mitochondrial depolarization and subsequent apoptosis in breast cancer cells. In addition, ultraviolet-visible spectroscopy and fluorescence quenching studies of the compound with tubulin confirmed direct interaction of compounds with tubulin. Molecular modeling studies revealed that it binds at the colchicine binding site in tubulin. Further, 2a also exhibited potent in vivo anticancer activity in LA-7 syngeneic rat mammary tumor model. Current data projects its strong candidature to be developed as anticancer agent.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. rpt.cdri@gmail.com rp_tripathi@cdri.res.in.
authors.forename: Kapil
authors.initials: K
authors.lastname: Upadhyaya
authors.lastname: Hamidullah
authors.forename: Kartikey
authors.initials: K
authors.lastname: Singh
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Arun
authors.forename: Mahendra
authors.initials: M
authors.lastname: Shukla
authors.forename: Neetika
authors.initials: N
authors.lastname: Srivastava
authors.forename: Raghib
authors.initials: R
authors.lastname: Ashraf
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.forename: Rohit
authors.initials: R
authors.lastname: Mahar
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Shukla
authors.forename: Jayanta
authors.initials: J
authors.lastname: Sarkar
authors.forename: Ravishankar
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
authors.forename: Rama Pati
authors.initials: RP
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005707:Gallic Acid / Q000737:chemistry / Q000494:pharmacology*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D058105:Polymerization / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006001:Glycoconjugates; D017382:Reactive Oxygen Species; D014404:Tubulin; D050257:Tubulin Modulators; D005707:Gallic Acid