Detailed Information on Publication Record
2022
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
HAVRÁNKOVÁ, Eva, V. GARAJ, S. MASCARETTI, A. ANGELI, Zuzana SOLDÁNOVÁ et. al.Basic information
Original name
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
Authors
HAVRÁNKOVÁ, Eva (203 Czech Republic, guarantor, belonging to the institution), V. GARAJ, S. MASCARETTI, A. ANGELI, Zuzana SOLDÁNOVÁ (203 Czech Republic, belonging to the institution), M. KEMKA, J. MOTYČKA, Marie BRÁZDOVÁ (203 Czech Republic, belonging to the institution), Jozef CSÖLLEI (203 Czech Republic, belonging to the institution), J. JAMPÍLEK and C.T. SUPURAN
Edition
International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2022, 1422-0067
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30104 Pharmacology and pharmacy
Country of publisher
Switzerland
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 5.600
RIV identification code
RIV/00216224:14160/22:00125425
Organization unit
Faculty of Pharmacy
UT WoS
000751345900001
Keywords in English
vancomycin-resistant enterococci; carbonic anhydrase; inhibition; triazine; benzenesulfonamide; stilbene; chalcone
Tags
International impact, Reviewed
Změněno: 23/2/2022 14:08, JUDr. Sabina Krejčiříková
Abstract
V originále
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.
Links
| MUNI/A/1202/2020, interní kód MU |
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