N-Substituted 2-(Benzenosulfonyl)-1-Carbotioamide Derivatives Exert Antimicrobial and Cytotoxic Effects via Aldehyde Dehydrogenase Pathway: Synthesis, In Silico and In Vitro Studies

Lucja Walczak-Nowicka; Anna Biernasiuk; Wojciech Ziemichód; Zbigniew Karczmarzyk; Mateusz Kwaśnik; Paweł Kozyra; Waldemar Wysocki; Agnieszka Stenzel-Bembenek; Dorota Kowalczuk; Mariola Herbet; Monika Pitucha

doi:10.3390/ph16121706

N-Substituted 2-(Benzenosulfonyl)-1-Carbotioamide Derivatives Exert Antimicrobial and Cytotoxic Effects via Aldehyde Dehydrogenase Pathway: Synthesis, In Silico and In Vitro Studies

Pharmaceuticals (Basel). 2023 Dec 8;16(12):1706. doi: 10.3390/ph16121706.

Affiliations

¹ Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland.
² Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.
³ Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
⁴ Institute of Chemistry, University of Siedlce, 3 Maja 54, 08-110 Siedlce, Poland.
⁵ Department of Molecular Biology, Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1J/4.03, 20-708 Lublin, Poland.
⁶ Department of Biochemistry and Molecular Biology, Faculty of Medical Sciences, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland.
⁷ Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.

Abstract

A series of N-Substituted 2-(benzenosulfonyl)-1-carbotioamide derivatives (WZ1-WZ4) were synthesized and characterized using spectral methods. A comprehensive activity study was performed for each compound. All compounds were tested for antibacterial activity. Moreover, in silico studies were carried out to determine the anticancer potential of the designed WZ1-WZ4 ligands. Based on molecular docking, aldehyde dehydrogenase was selected as a molecular target. The obtained data were compared with experimental data in vitro tests. Novel hybrids of the thiosemicarbazide scaffold and sulfonyl groups may have promising anticancer activity via the aldehyde dehydrogenase pathway. The best candidate for further studies appears to be WZ2, due to its superior selectivity in comparison to the other tested compounds.

Keywords: aldehyde dehydrogenase; anticancer: in silico; antimicrobial; docking; thiosemicarbazide.

Grants and funding

These studies were carried out as part of the Statutory Activity of the Medical University of Lublin, DS 16.