title: Anticancer activity, toxicity and pharmacokinetic profile of an indanone derivative.
abstract: The present study describes anticancer effect of gallic acid based indanone derivative (1). Indanone 1 exhibited in vivo anticancer activity against Erhlich ascites carcinoma in Swiss albino mice by inhibiting tumor growth by 54.3% at 50 mg/kg b.wt. It showed antitubulin effect by inhibiting tubulin polymerase enzyme. In cell cycle analysis, it inhibited G2/M phase and induced apoptosis. It significantly suppressed VEGF-R1, VEGF-R2 and HIF-α in human breast cancer MCF-7 cells, thus exhibiting antiangiogenic activity. In acute oral toxicity, indanone 1 was well tolerated and was found to be non-toxic up to 1000 mg/kg b.wt. in Swiss albino mice. Pharmacokinetic studies in rabbits revealed rate of absorption, half life, volume of distribution with high plasma and blood clearance after i.v. administration. Indanone 1, is a safe and moderately active anticancer agent.
authors.affiliation: Central Institute of Medicinal and Aromatic Plants, Lucknow, UP, India.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chanda
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Guru
authors.forename: Karuna
authors.initials: K
authors.lastname: Shanker
authors.forename: Z A
authors.initials: ZA
authors.lastname: Wani
authors.forename: B A
authors.initials: BA
authors.lastname: Rah
authors.forename: Suaib
authors.initials: S
authors.lastname: Luqman
authors.forename: Dilip M
authors.initials: DM
authors.lastname: Mondhe
authors.forename: Anirban
authors.initials: A
authors.lastname: Pal
authors.forename: Arvind S
authors.initials: AS
authors.lastname: Negi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D050257:Tubulin Modulators / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007189:Indans; D016328:NF-kappa B; D050257:Tubulin Modulators; C013352:indacrinone