Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin αvβ3/αIIbβ3 dual antagonists using 3D-QSAR and molecular docking.

摘要: Abstract The development of injectable integrin αvβ3/αIIbβ3 dual antagonists attracts much attention research for treating acute ischemic diseases in recent years. In this work, based on a dataset composed 102 tricyclic piperazine/piperidine furnished αvβ3 and αIIbβ3 antagonists, variety silico modeling approaches including the comparative molecular field analysis (CoMFA), similarity indices (CoMSIA), docking were applied to reveal requisite 3D structural features impacting biological activities. Our statistical results show that ligand-based 3D-QSAR models both studies exhibited satisfactory internal external predictability, i.e., CoMFA models, Q2 = 0.48, R ncv 2 = 0.87 , pred 0.71 Q2 = 0.50, 0.85 0.72 obtained, CoMSIA ones, outcomes Q2 = 0.55, 0.90 Q2 = 0.52, 0.88 0.74 achieved respectively. addition, through comparison between contour maps results, it is revealed most crucial interactions occurring derivatives receptor ligand binding pocket are H-bonding, key amino acids Arg214, Asn215, Ser123, Lys253 αvβ3, but Ser123 Tyr190 receptors, Halogen-containing groups at position 15 16, benzene sulfonamide substituent 23, replacement piperazine with 4-aminopiperidine ring B may increase antagonistic activity. potencies inhibit isolated linear correlated, indicating similar interaction mechanisms exist series molecules. To our best knowledge first report these antagonists. obtained should provide information better understanding mechanism antagonism thus be helpful design novel potent