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.

Inducible nitric oxide synthase: Regulation, structure, and inhibition

“…A 2014 report discusses a series of natural product‐like compounds discovered via high‐throughput virtual screening. One compound (bis‐indole 35 ) is proposed to be a competitive inhibitor of NO production in stimulated macrophages.…”

Discovery of a novel neuroprotectant, BHDPC, that protects against MPP+/MPTP-induced neuronal death in multiple experimental models

“…Through drug screening in this model, several compounds with neuroprotective effects such as iNOS inhibitors and anticancer agents have been successfully identified [34][35][36][37][38][39].…”

Hydrogen peroxide-promoted metal free oxidative amidation of 2-oxoaldehydes: a facile access to unsymmetrical oxamides

“…1 H and 13 C NMR spectra were measured on a Bruker Avance 400 or 600 MHz NMR spectrometer with CDCl 3 or DMSO-d 6 as solvent and recorded in ppm relative to an internal tetramethylsilane standard. Thin layer chromatography (TLC) characterization was performed with precoated silica gel GF254 (0.2 mm), while column chromatography characterization was performed with silica gel (100e200 mesh).…”

“…2 As an important and unique member of amides, oxamides also represents a key framework of many bioactive compounds. 3 They have been developed as acetylcholine esterase inhibitors, 4 C5a inhibitors, 5 nitric oxide synthase inhibitors, 6 anti-HIV agents, 7 antiepileptic drugs 8 and HIV integrase inhibitors 9 (Fig. 1).…”