QSAR and Docking Studies of N-hydroxy Urea Derivatives as Flap Endonuclease-1 Inhibitors

Title:QSAR and Docking Studies of N-hydroxy Urea Derivatives as Flap Endonuclease-1 Inhibitors

Volume: 11 Issue: 4

Author(s): Pankaj Wadhwa, Priti Jain and Hemant R. Jadhav

Affiliation:

Keywords: Cancer, QSAR, docking, flap endonuclease-1, glide, FEN-1.

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 R² of 0.806 and Q² 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.

Cite this article as:

Wadhwa Pankaj, Jain Priti and Jadhav R. Hemant, QSAR and Docking Studies of N-hydroxy Urea Derivatives as Flap Endonuclease-1 Inhibitors, Current Computer-Aided Drug Design 2015; 11 (4) . https://dx.doi.org/10.2174/1573409912666151124233628