Synthesis and biological evaluation of di- and tri-substituted imidazoles as safer anti-inflammatory-antifungal agents

Abstract

PURPOSE:In view of the potential pharmacophoric nature of imidazole nucleus, two series of imidazole derivatives, 2,4-disubstituted-1 H-imidazoles (2a-m) and 1,2,4-trisubstituted-1 H-imidazoles (3a-m), were synthesized with an aim of obtaining dual acting compounds i.e., anti-inflammatory and antifungal agents.MATERIALS AND METHODS:The title compounds were synthesized from 4-methoxyphenyl glyoxal (1) following multistep synthesis, and their structures were established on the basis of modern analytical techniques (IR, NMR and MS). The synthesized imidazoles were tested for their in vivo anti-inflammatory activity. In addition to that, some compounds were also evaluated for their analgesic and ulcerogenic effects. The compounds were also evaluated for their in vitro antifungal activity.RESULTS:Di- and tri-substituted imidazole derivatives (2a-m and 3a-m) were successfully synthesized. In in vivo anti-inflammatory test, six compounds (2 h, 2 l, 3 g, 3 h, 3 l and 3 m) exhibited good anti-inflammatory activity (49.58 to 58.02% inhibition) with minimal GI irritation (severity index; 0.17 to 0.34). These compounds were also tested for their analgesic activity and showed appreciable protection (40.53 to 49.60% protection) against saline-induced writhing test. Indomethacin was used as standard drug for comparison. In antifungal test, two compounds (3 h and 3 l) displayed appreciable antifungal activity (MIC; 12.5 μg mL-1) against the fungal strains tested.CONCLUSION:Two compounds, 2-(4-nitrophenyl)-4-(4-methoxyphenyl)-1-phenyl-1H-imidazole (3 h) and 2,4-di-(4-methoxyphenyl)-1-phenyl-1H-imidazole (3 l), emerged as lead compounds having dual biological activities; good anti-inflammatory as well as antifungal effect with lesser GI irritation.

Synthesis and Characterization of Novel Biginelli Dihydropyrimidinone Derivatives Containing Imidazole Moiety

“…To prepare the final dihydropyrimidinone derivatives, a mixture of substituted benzaldehyde (0.01 mol) III, enaminone (II) (0.01 mol), urea (0.01 mol) IV, and glacial acetic acid (10 mL) was heated under reflux for 3 hours. e precipitates of compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were collected by vacuum filtration. e product was washed several times with water and recrystallized from glacial acetic acid and ethanol mixture.…”

“…Numerous imidazole-based compounds as therapeutic drugs have been extensively used to treat various types of diseases. Many potent marketed drugs like ketoconazole, miconazole, clotrimazole, misonidazole, alpidem, flumazenil, metronidazole, luliconazole, dacarbazine, cimetidine, and clonidine contain imidazole moiety [1]. Imidazole-based compounds presents various biological activities, such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, and antiviral [2].…”

CoFe2O4 as green and efficient catalyst for synthesis of multisubstituted imidazoles

“…Numerous activity of multisubstituted imidazoles were reported in literatures. For example these compounds can act as therapeutic agents [13], ionic liquids [14][15][16], antiinflammatory [17,18], and antimicrobial reagent [19][20][21][22].…”

Design, synthesis, and biological evaluation of novel 1,2‐diaryl‐4‐substituted‐benzylidene‐5(4H)‐imidazolone derivatives as cytotoxic agents and COX‐2/LOX inhibitors

“…Derivatives of imidazole as example for five membered heterocyclic ring were reported to have multiple therapeutic and pharmacological actions such as antimicrobial, anticonvulsant, anticancer, anti‐inflammatory, and analgesic activities . Many drugs in the market have imidazole nucleus in their structures like metronidazole as antifungal, flumazenil as benzodiazepine antagonist, dacarbazine as anticancer, cimetidine as antihistaminics and ketoconazole and flutrimazole were found to have anti‐inflammatory activity in addition to their antifungal activity …”