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Heterocyclic compounds are one of the main groups of organic compounds possessing wide range of applications in various areas of science and their derivatives are present in many bioactive structures. They display a wide variety of biological activities. Recently, more and more attention has been focused to such heterocyclic compounds as azoles. In this work, we have synthesized a series of new imidazole derivatives incorporating a benzenesulfonamide moiety in their structure, which then were evaluated for their cytotoxicity against human triple-negative breast cancer MDA-MB-231 and human malignant melanoma IGR39 cell lines by MTT assay. Benzenesulfonamide-bearing imidazole derivatives containing 4-chloro and 3,4-dichlorosubstituents in benzene ring, and 2-ethylthio and 3-ethyl groups in imidazole ring have been determined as the most active compounds. Half-maximal effective concentration (EC50) of the most cytotoxic compound was 27.8 ± 2.8 µM against IGR39 cell line and 20.5 ± 3.6 µM against MDA-MB-231 cell line. Compounds reduced cell colony formation of both cell lines and inhibited the growth and viability of IGR39 cell spheroids more efficiently compared to triple-negative breast cancer spheroids.

A series of novel benzenesulfonamide derivatives were synthesized bearing para-N β,γ-amino acid or para-N β-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals. However, most of them bind to most CA isozymes with little selectivity. The design of high affinity and selectivity towards one CA isozyme remains a significant challenge. The beta and gamma amino acid-substituted compound affinities were determined by the fluorescent thermal shift assay and isothermal titration calorimetry for all 12 catalytically active human carbonic anhydrase isozymes, showing the full affinity and selectivity profile. The structures of several compounds were determined by X-ray crystallography, and the binding mode in the active site of CA enzyme was shown.

Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or S-alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant M. abscessus strains and compared their antimycobacterial activity using M. bovis BCG and M. tuberculosis H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound 13, containing 4-CF3 substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against M. abscessus complex strains, as well as M. bovis BCG and M. tuberculosis H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds.

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