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

• Published in: Journal of the Serbian Chemical Society 2022, Vol.87 (12), p.1381-1393
• Main Authors: Hou, Jing-Xuan, Gu, Qing-Shan, Shi, Mei-Qi, Gao, Hui, Lu, Zheng, Wu, Qing-Kun
• Format: Article
• Language: English
• Subjects: cancer; comfa; computational drug design; comsia
• ISSN: 0352-5139; 1820-7421
• DOI: 10.2298/JSC220510076H

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.