Coumarin–benzimidazole hybrids: A review of developments in medicinal chemistry

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.