RT Journal Article
T1 Bioactive imidamide-based compounds targeted against nitric oxide synthase.
A1 Arias, Fabio
A1 Franco-Montalban, Francisco
A1 Romero, Miguel
A1 Duarte, Juan
A1 Dora Carrion, M
A1 Encarnacion Camacho, M
K1 Imidamide
K1 Inducible nitric oxide synthase
K1 Neuronal nitric oxide synthase
K1 Nitric oxide synthase inhibitors
K1 Septic shock
K1 Synthesis
AB The selective inhibition of inducible nitric oxide synthase (iNOS) has become an interesting goal for the treatment of diseases where the immune and inflammatory response of the organism is involved. Septic shock is one prominent example of this type of affections. In this paper, the design and synthesis of twelve substituted pyridinyl- imidamide derivatives is described, together with their biological evaluation as NOS inhibitors. The most potent and selective compound was N-(3-hydroxy-3-(pyridin-3-yl)propyl)acetimidamide 9a (IC50 = 4.6 µM, against iNOS). Pharmacological assays in aortic rat tissue, have confirmed its inhibitory activity on iNOS and the absence of undesired cardicovascular effects. In silico analysis of the most promising compounds (9a, 9b, 9e and 9g) have predicted good drug-likeness properties. Furthermore, they have shown an adequate cell viability. Docking studies carried out on 9a suggest a particular binding mode that involves the essential residue Glu377, and might explain its iNOS selectivity. From a chemical point of view, the article describes an unusual cyclization to obtain pyridinyl-pyrimidine derivatives with high yield.
PB Academic Press
YR 2022
FD 2022-01-20
LK http://hdl.handle.net/10668/22034
UL http://hdl.handle.net/10668/22034
LA en
NO Arias F, Franco-Montalban F, Romero M, Duarte J, Dora Carrión M, Encarnación Camacho M. Bioactive imidamide-based compounds targeted against nitric oxide synthase. Bioorg Chem. 2022 Mar;120:105637.
NO The authors thank the Centro de Supercomputación de la Universidad de Granada (CSIRC) for the computing resources.This work was supported by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV) and by the Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R and PID2020-116347RB-100).The authors thank the Granada University Library for the financial support to the APC.
DS RISalud
RD Apr 18, 2025