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.

Facile Synthesis, Characterization and Antimicrobial Activity of 2-Alkanamino Benzimidazole Derivatives

“…The pharmacological investigation showed that the antagonism of Ang II-induced pressure response by oral administration of a series of benzimidazole hybrid was obviously superior to that of clinical drug standard used. This result suggested that NO-releasing benzimidazole hybrids may provide a promising approach for the discovery of 23 . Benzimidazole derivatives were recently reviewed as target agents for antidiabetic by different mechanisms such as peroxisome proliferator-activated receptor á-transcriptional activity, glycosidases receptor, dipeptidyl peptidase IV, glucokinase, human glucagon receptor (hGCGR) antagonist, aldose reductase enzyme and stearoyl-CoA desaturase 24 .…”

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

“…Two series of nitric oxide (NO) releasing benzimidazole derivatives were synthesized by coupling benzimidazole biphenyl skeleton with nitro ester and furoxan NO-donor moieties, where compounds 393–394 were reported to possess comparable activity to positive control losartan ( Zhang et al, 2015 ). Hao et al ( Hao et al, 2015 ) designed and synthesized a series of 4′-[(benzimidazol-1-yl)methyl]biphenyl-2-sulphonamide derivatives and reported that compound 395 was found to be the most potent AT 1 and Endothelin ET A receptor antagonist with IC 50 values 28 and 10 nM, respectively.…”

Preparation of Benzimidazole Based Coumarin Derivatives as Antimicrobial and Antioxidant Agents

“…4 Accordingly, it is worthy to develop new medicinal compounds possessing appreciable antioxidant activity for the management of microbial infections. Benzimidazoles and coumarins are reported as antibmicrobial 5 , antiviral 6 , antidiabetic 7,8 , antihypertensive 9,10 , antitumor 11 , and antioxidants 12,13 . In light of the literature, it looked worthful that a combination of benzimidazole moiety and coumarin moiety may provide medicinal compounds that possess appreciable antioxidant activity as well as antimicrobial potential.…”