title: Chemical inhibition of fatty acid synthase: molecular docking analysis and biochemical validation in ocular cancer cells.
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 IC(50) 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.
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology & Science (BITS), Pilani, PS Division, Chennai Centre, 5, Montieth Lane, Egmore, Chennai, 600 008 India.
authors.forename: P R
authors.initials: PR
authors.lastname: Deepa
authors.forename: S
authors.initials: S
authors.lastname: Vandhana
authors.forename: S
authors.initials: S
authors.lastname: Muthukumaran
authors.forename: V
authors.initials: V
authors.lastname: Umashankar
authors.forename: U
authors.initials: U
authors.lastname: Jayanthi
authors.forename: S
authors.initials: S
authors.lastname: Krishnakumar