title: Design, synthesis and pharmacological evaluation of novel NO-releasing benzimidazole hybrids as potential antihypertensive candidate.
abstract: Two series of novel NO-releasing benzimidazole derivatives (8a-e, 9a-g) were designed and synthesized by coupling nitro ester and furoxan NO-donor moieties with benzimidazole biphenyl skeleton. The NO-releasing assay indicated that all the target compounds had different level of NO-releasing ability. Furthermore, the isolated organ assay (rat aortic strips) was used to evaluate the antagonism of Ang II-induced vasoconstriction ability. It was observed that the pA2 values of compounds 8e and 9e were better than that of lead compound 6. Moreover, the pharmacological investigation showed that the antagonism of Ang II-induced pressure response by oral administration of compound 8e was obviously superior to that of lead compound 6, and comparable to that of the positive control losartan. These results suggested that NO-releasing hybrids may provide a promising approach for the discovery of novel antihypertensive agents.
authors.affiliation: Department of Medicinal Chemistry, Anhui University of Chinese Medicine, 103 Meishan Road, Hefei, 230031, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D020030:Nitric Oxide Donors; D000804:Angiotensin II; D009569:Nitric Oxide; C031000:benzimidazole; D019808:Losartan
keywords: Ang II antagonism; antihypertension; benzimidazole derivatives; nitric oxide (NO)