Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo

• Main Authors: Zhong, Hai-Jing, Liu, Li-Juan, Chong, Cheong-Meng, Lu, Lihua, Wang, Modi, Chan, Daniel Shiu-Hin, Chan, Philip Wai Hong, Lee, Simon Ming-Yuen, Ma, Dik-Lung, Leung, Chung-Hang
• Other Authors: Verma, Chandra
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science
• Online Access: https://hdl.handle.net/10356/80047; http://hdl.handle.net/10220/19501
• Institution: Nanyang Technological University

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.