Discovery of a Natural Product-Like iNOS Inhibitor by Molecular Docking with Potential Neuroprotective Effects In Vivo
|
| |
| Authors: | Hai-Jing Zhong Li-Juan Liu Cheong-Meng Chong Lihua Lu Modi Wang Daniel Shiu-Hin Chan Philip Wai Hong Chan Simon Ming-Yuen Lee Dik-Lung Ma Chung-Hang Leung |
| |
| Institution: | 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.; 2. Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.; 3. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.; Bioinformatics Institute, Singapore, |
| |
| Abstract: | In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS. The iNOS inhibitory activity of the hit compounds was characterized using cellular assays and an in vivo zebrafish larvae model. The natural product-like compound 1 inhibited NO production in LPS-stimulated Raw264.7 macrophages, without exerting cytotoxic effects on the cells. Significantly, compound 1 was able to reverse MPTP-induced locomotion deficiency and neurotoxicity in an in vivo zebrafish larval model. Hence, compound 1 could be considered as a scaffold for the further development of iNOS inhibitors for potential anti-inflammatory or anti-neurodegenerative applications. |
| |
| Keywords: | |
|
|
