Journal Article

PUBDB-2025-02292

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Novel Derivatives of 3-Amino-4-hydroxy-benzenesulfonamide: Synthesis, Binding to Carbonic Anhydrases, and Activity in Cancer Cell 2D and 3D Cultures

Vainauskas, V. ; Norvaišaitė, R. ; Grybaitė, B. ; Vaickelionienė, R. ; Smirnov, A. ; Kojis, T. ; Baranauskiene, L. ; Manakova, E. ; Gražulis, S. ; Zubrienė, A. ; Matulis, D. ; Mickevičius, V. (Corresponding author) ; Petrikaitė, V. (Corresponding author)

2025
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms26136466  doi:10.3204/PUBDB-2025-02292

Abstract: first_pagesettingsOrder Article ReprintsOpen AccessArticleNovel Derivatives of 3-Amino-4-hydroxy-benzenesulfonamide: Synthesis, Binding to Carbonic Anhydrases, and Activity in Cancer Cell 2D and 3D Culturesby Valdas Vainauskas1, Rugilė Norvaišaitė2, Birutė Grybaitė1 [ORCID] , Rita Vaickelionienė1, Alexey Smirnov2, Tautvydas Kojis2 [ORCID] , Lina Baranauskiene2 [ORCID] , Elena Manakova3 [ORCID] , Saulius Gražulis4, Asta Zubrienė2 [ORCID] , Daumantas Matulis2 [ORCID] , Vytautas Mickevičius1,* [ORCID] and Vilma Petrikaitė5,6,*1Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų Rd. 19, LT-50254 Kaunas, Lithuania2Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, LT-10257 Vilnius, Lithuania3Department of Protein–DNA Interactions, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio al. 7, LT-10257 Vilnius, Lithuania4Sector of Crystallography and Chemical Informatics, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio al. 7, LT-10257 Vilnius, Lithuania5Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, LT-10257 Vilnius, Lithuania6Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių 13, LT-50162 Kaunas, Lithuania*Authors to whom correspondence should be addressed.Int. J. Mol. Sci. 2025, 26(13), 6466; https://doi.org/10.3390/ijms26136466Submission received: 3 June 2025 / Revised: 30 June 2025 / Accepted: 1 July 2025 / Published: 4 July 2025(This article belongs to the Special Issue New Players in the Research of Oxidative Stress and Cancer)Downloadkeyboard_arrow_downBrowse FiguresVersions NotesAbstractA series of novel derivatives of 3-amino-4-hydroxybenzenesulfonamide was synthesized. As the analyzed compounds possess a sulfonamide group, the affinity of these compounds for human carbonic anhydrases (CAs) was measured by fluorescent thermal shift assay, and compound selectivity for different isoenzymes was identified. The crystal structures of the complexes of compound 25 with CAI and CAII were determined. Additionally, the activity of compounds on the viability of three cancer cell lines—human glioblastoma U-87, triple-negative breast cancer MDA-MB-231, and prostate adenocarcinoma PPC-1—was established using the MTT assay and compared to CAIX-selective and non-selective comparative compounds U-104 and acetazolamide. The half-maximal concentration (EC50) was determined for the identified most active compounds, and their selectivity over fibroblasts was established. Compound 9 (inhibitor of multi-CAs) and compound 21 (not binding to CAs), considered the most promising candidates, were tested in cancer cell 3D cultures (cancer spheroids) by assessing their effect on spheroid growth and viability. Both compounds reduced the viability of spheroids from all cancer cell lines. U-87 and PPC-1 spheroids became looser in the presence of compound 9, while the growth of MDA-MB-231 spheroids was slower compared to the control. Compound 21 reduced the growth of U-87 and MDA-MB-231 3D cultures, with no significant effect on PPC-1 spheroids.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2025

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