title: Quantitative structure activity relationship studies of piperazinyl phenylalanine derivatives as VLA-4/VCAM-1 inhibitors.
abstract: QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r2=0.85) was selected for further study and the resulted validation parameters of the model, crossed squared correlation coefficient (q2=0.76 and pred_r2=0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcount slogP,and 4PathCount are highly correlated with VLA-4/VCAM-1 inhibitory activity of piperazinyl phenylalanine derivatives. The result of the study suggests that the chlorine atoms in the molecule and fourth order fragmentation patterns in the molecular skeleton favour VLA-4/VCAM-1 inhibition shown by the title compounds whereas lipophilicity and nitrogen bonded to aromatic bond are not conducive for VLA-4/VCAM-1 inhibitory activity.
authors.affiliation: School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal-462036, Madhya Pradesh, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Bhargava
authors.forename: C
authors.initials: C
authors.lastname: Karthikeyan
authors.forename: N S H N
authors.initials: NS
authors.lastname: Moorthy
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D006801:Humans; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D019169:Jurkat Cells; D010649:Phenylalanine / Q000737:chemistry* / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D039041:Integrin alpha4beta1; D010879:Piperazines; D019010:Vascular Cell Adhesion Molecule-1; D000077489:Piperazine; D010649:Phenylalanine