Biological Activity of Newly Synthesized Benzimidazole and Benzothizole 2,5-Disubstituted Furane Derivatives

Abstract

Newly designed and synthesized cyano, amidino and acrylonitrile 2,5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity. For potential antitumor activity, the compounds were tested in 2D and 3D cell culture methods on three human lung cancer cell lines, A549, HCC827 and NCI-H358, with MTS cytotoxicity and BrdU proliferation assays in vitro. Compounds 5, 6, 8, 9 and 15 have been proven to be compounds with potential antitumor activity with high potential to stop the proliferation of cells. In general, benzothiazole derivatives were more active in comparison to benzimidazole derivatives. Antimicrobial activity was evaluated with Broth microdilution testing (according to CLSI (Clinical Laboratory Standards Institute) guidelines) on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, Saccharomyces cerevisiae was included in testing as a eukaryotic model organism. Compounds 5, 6, 8, 9 and 15 showed the most promising antibacterial activity. In general, the compounds showed antitumor activity, higher in 2D assays in comparison with 3D assays, on all three cell lines in both assays. In natural conditions, compounds with such an activity profile (less toxic but still effective against tumor growth) could be promising new antitumor drugs. Some of the tested compounds showed antimicrobial activity. In contrast to ctDNA, the presence of nitro group or chlorine in selected furane-benzothiazole structures did not influence the binding mode with AT-DNA. All compounds dominantly bound inside the minor groove of AT-DNA either in form of monomers or dimer and higher-order aggregates.

Recent insights into antibacterial potential of benzothiazole derivatives

“…SAR study indicated that the placement of isopropylamide ( 107a and 107c ) and 4,5-dihydro-1H-imidazol-2-yl ( 107b and 107d ) moieties at the 5th position of benzothiazole ring improved the antibacterial activity. The existence of nitro ( 107a and 107b ) and chloro ( 107c and 107d ) groups at the para -position of the phenyl ring improved the bacterial inhibition [ 66 ].

Scheme 23 The chemical reaction involved in the preparation of 2,5-disubstituted furan benzothiazole derivatives ( 107a-d )

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Revolutionizing Antimicrobial Drug Discovery: Computational Design and Admet Studies of Emerging Potent Anti-Microbial Agents

“…It has demonstrated efficacy as an antidiabetic, antiulcer, antiinflammatory, anticancer, antiviral, and antimicrobial agent [10]. Numerous studies have underscored the antimicrobial potential of benzimidazole derivatives against various microorganisms [11][12][13][14].…”

Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines

“…Therefore, a focus in this particular discipline involves the creation and development of new anticancer medications with greater cytotoxic efficacy against cancer cells and minimal side effects. Due to their capacity to interact with a variety of different enzymes and receptors, benzimidazoles are well known as biologically significant chromophores in medicinal chemistry (2). Transition metal complexes of such biologically significant ligands exhibit better pharmacological activity than the corresponding free ligand.…”