title: QSAR and Docking Studies of N-hydroxy Urea Derivatives as Flap Endonuclease-1 Inhibitors.
abstract: Flap endonuclease-I (FEN-1) is involved in DNA repair and considered to be a novel target for the development of anticancer agents. N-hydroxy urea derivatives have been reported as FEN-1 inhibitors. To derive in vitro and in silico correlation, we have performed 2D-quantitative structure activity relationship (QSAR) analysis and docking studies on these compounds. 2D-QSAR models were developed using multiple linear regression (MLR) analysis and cross-validation using leave one out (LOO) method. The best model displayed R(2) of 0.806 and Q(2) of 0.607. Docking study revealed key interactions with desired amino acids and compare well with the in vitro potency of the reported compounds. Both studies reveal a link between FEN-1 inhibition and physicochemical descriptors or interactions with amino acids in active site. The information generated is first of its kind and may be helpful in the design of novel FEN-1 inhibitors.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Wadhwa
authors.forename: Priti
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani campus, Vidya Vihar, Pilani - 333 031, Rajasthan, India. hemantrj@pilani.bits-pilani.ac.in.
authors.forename: Hemant R
authors.initials: HR
authors.lastname: Jadhav
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D045585:Flap Endonucleases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000737:chemistry* / Q000494:pharmacology*; D016014:Linear Models; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D045585:Flap Endonucleases; D006918:Hydroxyurea