title: Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities.
abstract: Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.
authors.affiliation: Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, India.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Bansal
authors.forename: Om
authors.initials: O
authors.lastname: Silakari
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004487:Edema / Q000188:drug therapy; D005260:Female; D006386:Hemagglutination Tests; D056724:Immunity, Humoral / Q000187:drug effects; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced; D023382:Toxicity Tests, Acute
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001562:Benzimidazoles; D007155:Immunologic Factors