An explorative study on potent Gram-negative specific LpxC inhibitors: CoMFA, CoMSIA, HQSAR and molecular docking. (4th March 2018) - Shiri, Fereshteh
Abstract: Pathogenic Gram-negative bacteria are responsible for nearly half of the serious human infections. Hologram quantitative structure–activity relationships (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) were implemented on a group of 32 of potent Gram-negative LpxC inhibitors. The most effective HQSAR model was obtained using atoms, bonds, donor, and acceptor as fragment distinction. The cross-validated correlation coefficient ( q 2 ), non-cross-validated correlation coefficient ( r 2 ), and predictive correlation coefficient ( r 2 Pred ) for test set of HQSAR model were 0.937, 0.993, and 0.892, respectively. The generated models were found to be statistically significant as the CoMFA model had ( r 2 = 0.967, q 2 = 0.804, r 2 Pred = 0.827); the CoMSIA model had ( r 2 = 0.963, q 2 = 0.752, r 2 Pred = 0.857). Molecular docking was employed to validate the results of the HQSAR, CoMFA, and CoMSIA models. Based on the obtained information, six new LpxC inhibitors have been designed.