3D-QSAR and molecular docking studies of aminothiazole derivatives as Lim kinase 1 inhibitors Scientific paper

Abstract

Lim kinase (Limk), as an important cytoskeletal regulator, plays an important role in cancer manifestations and neuronal diseases. Limk1 is a mem­ber of the Limk family, which is mainly involved in the invasion and metastasis of tumor cells and is abnormally expressed in a variety of cell carcinoma tissues. In this paper, a series of Limk1 inhibitors with amino­thia­zole skeleton were used to design potent and efficient Limk1 inhibitors by computational approaches. Firstly, the 3D-QSAR model was constructed, and both CoMFA and CoMSIA models have good correlation and prediction abil­ity. The binding requirements between ligand and receptor protein were then further explored through mole­cular docking, including the critical forces between Limk1 inhibitors and active site residues. Finally, based on the 3D-QSAR model and molecular docking results analysis, three new compounds with theoretically better activity were des­igned and their ADME properties were predicted.