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

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; Edmond Dik Lung MA; Chung Hang Leung

doi:10.1371/journal.pone.0092905

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

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, Edmond Dik Lung MA, Chung Hang Leung

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

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.

Original language	English
Article number	e92905
Journal	PLoS ONE
Volume	9
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0092905
Publication status	Published - 1 Apr 2014

Scopus Subject Areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
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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.",

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AU - Zhong, Hai Jing

AU - Liu, Li Juan

AU - Chong, Cheong Meng

AU - Lu, Lihua

AU - Wang, Modi

AU - Chan, Daniel Shiu Hin

AU - Chan, Philip Wai Hong

AU - Lee, Simon Ming Yuen

AU - MA, Edmond Dik Lung

AU - Leung, Chung Hang

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AB - 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.

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

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