1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study
Danuta Branowska,
Zbigniew Karczmarzyk,
Ewa Wolińska,
Waldemar Wysocki,
Maja Morawiak,
Zofia Urbańczyk-Lipkowska,
Anna Bielawska,
Krzysztof Bielawski
Affiliations
Danuta Branowska
Faculty of Exact and Natural Sciences, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland
Zbigniew Karczmarzyk
Faculty of Exact and Natural Sciences, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland
Ewa Wolińska
Faculty of Exact and Natural Sciences, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland
Waldemar Wysocki
Faculty of Exact and Natural Sciences, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland
Maja Morawiak
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Zofia Urbańczyk-Lipkowska
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Anna Bielawska
Medical University of Bialystok, Department of Medicinal Chemistry and Drug Technology, J. Kilinskiego 1, 15-089 Bialystok, Poland
Krzysztof Bielawski
Medical University of Bialystok, Department of Medicinal Chemistry and Drug Technology, J. Kilinskiego 1, 15-089 Bialystok, Poland
In this study, we synthesized novel sulfonamides with a 1,2,4-triazine moiety according to pharmacophore requirements for biological activity. All the synthesized compounds were tested in vitro to verify whether they exhibited anticancer activity against the human breast cancer cell lines MCF-7 and MDA-MB-231. Among them, two most active ones, having IC50 values of 50 and 42 µM, respectively, were found to show higher anticancer activity than chlorambucil used as the reference in the in vitro tests. In addition, two other compounds, which had IC50 values of 78 and 91 µM, respectively, exhibited a similar level of activity as chlorambucil. X-ray analysis carried out for two of the compounds confirmed their synthesis pathway as well as their assumed molecular structures. Furthermore, a conformational analysis was performed, and electronic parameters of molecules were characterized using theoretical calculations at AM1 and DFT level. Moreover, molecular docking revealed the mode of binding of the investigated 1,2,4-triazine sulfonamides with the human estrogen receptor alpha (ERα).
