Discovery of a Natural Product-Like iNOS Inhibitor by Molecular Docking with Potential Neuroprotective Effects In Vivo

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.

Discovery of a Natural Product-Like iNOS Inhibitor by Molecular Docking with Potential Neuroprotective Effects In Vivo

Hai-Jing Zhong equal contributor, Li-Juan Liu equal contributor, 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.

Part of this publication was performed with ZebraLab and ZebraBox