title: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Cheong-Meng
authors.initials: CM
authors.lastname: Chong
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Modi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Daniel Shiu-Hin
authors.initials: DS
authors.lastname: Chan
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Philip Wai Hong
authors.initials: PW
authors.lastname: Chan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001688:Biological Products / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D007527:Isoenzymes / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000502:physiology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000032:analysis / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000067996:RAW 264.7 Cells; D013816:Thermodynamics; D015027:Zebrafish
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D052247:Nitric Oxide Synthase Type II