RT Journal Article
T1 Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors.
A1 Arias, Fabio
A1 Franco-Montalban, Francisco
A1 Romero, Miguel
A1 Carrión, M Dora
A1 Camacho, M Encarnación
K1 Drug design
K1 Imidamides
K1 Inhibitors
K1 Nitric Oxide Synthase
K1 Synthesis
AB In search of new Nitric Oxide Synthase (NOS) inhibitor agents, two isosteric series of derivatives with an imidamide scaffold (one of them with a hydroxyl group and the other with a carbonyl one) were synthesized and evaluated on inducible (iNOS) and neuronal (nNOS) isoforms. These compounds have been designed by combining a kynurenamine framework with an amidine moiety in order to improve selectivity for the inducible isoform. In general, the in vitro inhibitory assays exhibited better inhibition values on the iNOS isoform, being the N-(3-(2-amino-5-methoxyphenyl)-3-hydroxypropyl)-4-(trifluoromethyl)benzimidamide 4i the most active inhibitor with the highest iNOS selectivity, without inhibiting eNOS. Docking studies on the two most active compounds suggest a different binding mode on both isozymes, supporting the experimentally observed selectivity towards the inducible isoform. Physicochemical in silico studies suggest that these compounds possess good drug-likeness properties.
YR 2021
FD 2021-06-28
LK https://hdl.handle.net/10668/27995
UL https://hdl.handle.net/10668/27995
LA en
DS RISalud
RD Apr 6, 2025