title: Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer.
abstract: Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3',4',5'-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4˝-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC50=3-10 μm) against several human cancer cell lines through microtubule destabilization (IC50=1.54 μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30 mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300 mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Aastha
authors: A
authors: Singh
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Kaneez
authors: K
authors: Fatima
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Ankita
authors: A
authors: Srivastava
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Sadiya
authors: S
authors: Khwaja
authors: CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Jammu, Jammu and Kashmir, India.
authors: Dev
authors: D
authors: Priya
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Arjun
authors: A
authors: Singh
authors: CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Jammu, Jammu and Kashmir, India.
authors: Girish
authors: G
authors: Mahajan
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Sarfaraz
authors: S
authors: Alam
authors: Amity University, Lucknow, Uttar Pradesh, India.
authors: Ajit K
authors: AK
authors: Saxena
authors: CSIR-Indian Institute of Integrative Medicine (CSIR-IIIM), Jammu, Jammu and Kashmir, India.
authors: D M
authors: DM
authors: Mondhe
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Suaib
authors: S
authors: Luqman
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Debabrata
authors: D
authors: Chanda
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India.
authors: Feroz
authors: F
authors: Khan
authors: CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow, Uttar Pradesh, India. arvindcimap@rediffmail.com.
authors: Arvind S
authors: AS
authors: Negi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000737:chemistry; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000097:blood; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005707:Gallic Acid / Q000737:chemistry*; D006801:Humans; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D014408:Biomarkers, Tumor; D007189:Indans; D014404:Tubulin; D050257:Tubulin Modulators; D005707:Gallic Acid
keywords: Ehrlich ascite carcinoma; benzylidene indanone; cell cycle; cytotoxicity; tubulin polymerization inhibition