title: Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.
abstract: Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.
authors.affiliation: Indian Institute of Integrative Medicine, Jammu 180001, J&K, India. amitnargotra@yahoo.com
authors.forename: Amit
authors.initials: A
authors.lastname: Nargotra
authors.forename: Sujata
authors.initials: S
authors.lastname: Sharma
authors.forename: Jawahir Lal
authors.initials: JL
authors.lastname: Koul
authors.forename: Pyare Lal
authors.initials: PL
authors.lastname: Sangwan
authors.forename: Inshad Ali
authors.initials: IA
authors.lastname: Khan
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: Subhash Chander
authors.initials: SC
authors.lastname: Taneja
authors.forename: Surrinder
authors.initials: S
authors.lastname: Koul
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052117:Benzodioxoles / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D052117:Benzodioxoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C075040:NorA protein, Staphylococcus; C008922:piperine