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@article{1836417,
author = {Havránková, Eva and Garaj, V. and Mascaretti, S. and Angeli, A. and Soldánová, Zuzana and Kemka, M. and Motyčka, J. and Brázdová, Marie and Csöllei, Jozef and Jampílek, J. and Supuran, C.T.},
article_location = {Basel},
article_number = {1},
doi = {http://dx.doi.org/10.3390/ijms23010231},
keywords = {vancomycin-resistant enterococci; carbonic anhydrase; inhibition; triazine; benzenesulfonamide; stilbene; chalcone},
language = {eng},
issn = {1422-0067},
journal = {International Journal of Molecular Sciences},
title = {Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors},
url = {https://www.mdpi.com/1422-0067/23/1/231},
volume = {23},
year = {2022}
}
TY - JOUR
ID - 1836417
AU - Havránková, Eva - Garaj, V. - Mascaretti, S. - Angeli, A. - Soldánová, Zuzana - Kemka, M. - Motyčka, J. - Brázdová, Marie - Csöllei, Jozef - Jampílek, J. - Supuran, C.T.
PY - 2022
TI - Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors
JF - International Journal of Molecular Sciences
VL - 23
IS - 1
SP - 1-45
EP - 1-45
PB - Multidisciplinary Digital Publishing Institute
SN - 14220067
KW - vancomycin-resistant enterococci
KW - carbonic anhydrase
KW - inhibition
KW - triazine
KW - benzenesulfonamide
KW - stilbene
KW - chalcone
UR - https://www.mdpi.com/1422-0067/23/1/231
N2 - A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with K(I)s = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 mu M) and derivative 32 (MIC range 13.80-55.20 mu M) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4'-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 mu M; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 mu M. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically alpha-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.
ER -
HAVRÁNKOVÁ, Eva, V. GARAJ, S. MASCARETTI, A. ANGELI, Zuzana SOLDÁNOVÁ, M. KEMKA, J. MOTYČKA, Marie BRÁZDOVÁ, Jozef CSÖLLEI, J. JAMPÍLEK and C.T. SUPURAN. Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol.~23, No~1, p.~1-45. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms23010231.
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