ascorbic-acid and benzimidazole

Coumarin and benzimidazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The pharmacokinetic and pharmacodynamic properties of the individual scaffolds can be improved by developing coumarin-benzimidazole chimeric molecules via molecular hybridization approach. The three major classes of coumarin-benzimidazole hybrids are merged, fused and spacer-linked hybrids. Depending on the substitution position, fused hybrids and spacer-linked hybrids can be further classified as coumarin-C3 hybrids, coumarin-C4 hybrids and coumarin-C5/6/7/8 hybrids. Most of the coumarin-benzimidazole hybrid molecules exhibited potent anticancer, antiviral, antimicrobial, antitubercular, anthelmintic, anti-inflammatory, antioxidant, anticonvulsant and carbonic anhydrase inhibitory activities. The fused coumarin-C3 hybrid (2), thiomethylene-linked coumarin-C3 hybrid (45), N-glucoside substituted thiomethylene-linked coumarin-C3 hybrid (37c), amide-linked coumarin-C3 hybrid (50a), and sulfonylmethylene-linked coumarin-C4 hybrid (63) were identified as the representative potent anticancer, antimicrobial, antiviral, antioxidant and antitubercular agents respectively. The biological properties of the different classes of coumarin-benzimidazole hybrids with their structure-activity relationship studies and the mechanism of action studies were presented in this review, aiming to help the researchers across the globe to generate future hybrid molecules as potential drug candidates.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Benzimidazoles; Chemistry, Pharmaceutical; Coumarins; Drug Development; Humans; Molecular Structure

A series of 5-methanesulphonamido benzimidazole derivatives were designed by combining the structural features of clinically useful anti-inflammatory drugs (nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.) based on physicochemical and 3D similarity studies. The compounds were evaluated for their anti-inflammatory activity in carrageenan induced rat paw edema model taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant activity of the compounds was assessed by potassium ferricyanide reducing power (PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity comparable to the standard group and were also non-ulcerogenic at the test doses. Compounds 6-11 exhibited good antioxidant effect in the concentration range (1.0-50.0µmol/ml. Preliminary theoretical ADME profiling of the compounds based on computation of selected physicochemical properties showed an excellent compliance with Lipinski's rule.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Benzimidazoles; Carrageenan; Dose-Response Relationship, Drug; Edema; Molecular Structure; Rats; Stomach Ulcer; Structure-Activity Relationship; Sulfonamides

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Female; Glaucoma; Humans; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Rats; Recombinant Proteins; rho-Associated Kinases; Structure-Activity Relationship

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Benzimidazoles; Brain; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Electrophorus; Ferrous Compounds; Horses; Mannich Bases; Molecular Docking Simulation; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Structure-Activity Relationship