Anticancer activity and toxicity profiles of 2-benzylidene indanone lead molecule

Eur J Pharm Sci. 2015 Aug 30:76:57-67. doi: 10.1016/j.ejps.2015.04.020. Epub 2015 Apr 29.

Abstract

3-(3',4',5'-Trimethoxyphenyl)-4,5,6-trimethoxy,2-(3″,4″-methylenedioxybenzylidene)-indan-1-one (1) is an optimized anti-cancer lead molecule obtained on modification of gallic acid, a plant phenolic acid. It exhibited potent cytotoxicities (IC50=0.010-14.76μM) against various human carcinoma cells. In cell cycle analysis, benzylidene indanone 1 induced G2/M phase arrest in both MCF-7 and MDA-MB-231 cells. It also induced apoptosis in DU145 cells which was evident by cleavage of PARP. In Ehrlich ascites carcinoma, benzylidene indanone 1 showed 45.48% inhibition of tumour growth at 20mg/kg dose in Swiss albino mice. Further, in sub-acute toxicity experiment in Swiss-albino mice, it was found to be non-toxic up to 100mg/kg dose for 28days. The lead compound benzylidene indanone 1 can further be optimized for better anti-cancer activity.

Keywords: 5-Fluorouracil (PubChem CID: 3385); Anticancer; Benzylidene indanone; Caspase; Cell cycle; Colchicine (PubChem CID: 6167); Combretastatin A4 (PubChem CID: 5351344); Ehrlich ascites carcinoma; Gallic acid (PubChem CID: 370); Piperonal (PubChem CID: 8438); Podophyllotoxin (PubChem CID: 10607); Sub-acute toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Benzodioxoles / pharmacology*
  • Benzodioxoles / toxicity
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / enzymology
  • Carcinoma, Ehrlich Tumor / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Indans / pharmacology*
  • Indans / toxicity
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Male
  • Poly Adenosine Diphosphate Ribose / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Time Factors
  • Tumor Burden / drug effects

Substances

  • 3-(3',4',5'-trimethoxyphenyl)-4,5,6-trimethoxy,2-(3',4'-methylenedioxybenzylidene)indan-1-one
  • Antineoplastic Agents
  • Benzodioxoles
  • Indans
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases