TY - JOUR
T1 - Discovery of a natural product-like iNOS inhibitor by molecular docking with potential neuroprotective effects in vivo
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
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84898874644&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0092905
DO - 10.1371/journal.pone.0092905
M3 - Journal article
C2 - 24690920
AN - SCOPUS:84898874644
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e92905
ER -
