Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors
| العنوان: | Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors |
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| المؤلفون: | Arias, Fabio, Franco Moltabán, Francisco, Romero Pérez, Miguel, Carrión Peregrina, María Dora, Camacho Quesada, Encarnación |
| المصدر: | Digibug. Repositorio Institucional de la Universidad de Granada instname |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Synthesis, Inhibitors, Nitric Oxide Synthase, Imidamides, Drug design |
| الوصف: | This work was supported by the grant from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R), with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV). The authors also thank the Centro de Supercomputación de la Universidad de Granada (CSIRC) for the computing resources and the Granada University Library for the financial support to the APC. 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. CSIRC Centro de Supercomputación de la Universidad de Granada Granada University Library European Commission Ministerio de Economía y Competitividad SAF2017-84894-R Instituto de Salud Carlos III Comisión Interministerial de Ciencia y Tecnología |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::a6ae3d3e7defa52c479607af6f2ed6a5 http://hdl.handle.net/10481/71721 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.dedup.wf.001..a6ae3d3e7defa52c479607af6f2ed6a5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |