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Journal of Ocular Biology, Diseases, and Informatics

Published in:

01-12-2010

Chemical inhibition of fatty acid synthase: molecular docking analysis and biochemical validation in ocular cancer cells

Authors: P. R. Deepa, S. Vandhana, S. Muthukumaran, V. Umashankar, U. Jayanthi, S. Krishnakumar

Published in: Journal of Ocular Biology, Diseases, and Informatics | Issue 4/2010

Abstract

Fatty acid biosynthesis is an attractive target for anti-cancer therapeutics. The ocular cancer, retinoblastoma cells were treated with fatty acid synthase (FASN) enzyme inhibitors: cerulenin, triclosan and orlistat. The IC₅₀ and dose-dependent sensitivity of cancer cells to FASN inhibitors decrease in biologic enzyme activity, and cell morphology alterations were analysed. Molecular interactions of enzyme-inhibitor complexes were studied by molecular modelling and docking simulations. The crystal structures of ketoacyl synthase (PDB ID:3HHD) (cerulenin) and thioesterase (PDB ID:2PX6) (orlistat) domains of human FASN were utilized for docking, while for the non-crystallised human FASN enoyl reductase domain (triclosan), homology model was built and used for docking. All three inhibitors showed significant binding energy indicating stable complex formation with their respective FASN subunits. The predicted Ki value of the FASN inhibitors corroborated well with their corresponding anti-cancer effects.

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Title: Chemical inhibition of fatty acid synthase: molecular docking analysis and biochemical validation in ocular cancer cells
Authors: P. R. Deepa
S. Vandhana
S. Muthukumaran
V. Umashankar
U. Jayanthi
S. Krishnakumar
Publication date: 01-12-2010
Publisher: Springer-Verlag
Published in: Journal of Ocular Biology, Diseases, and Informatics / Issue 4/2010
Electronic ISSN: 1936-8445
DOI: https://doi.org/10.1007/s12177-011-9065-7

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Chemical inhibition of fatty acid synthase: molecular docking analysis and biochemical validation in ocular cancer cells

Abstract

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