NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT
CARBONIC ANHYDRASE INHIBITORS

k 2023

NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS

HAVRÁNKOVÁ, Eva, Jozef CSÖLLEI, Karolína ŠELIGOVÁ and C.T. SUPURAN

Basic information

Original name

NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS

Authors

HAVRÁNKOVÁ, Eva (203 Czech Republic, guarantor, belonging to the institution), Jozef CSÖLLEI (703 Slovakia, belonging to the institution), Karolína ŠELIGOVÁ (203 Czech Republic, belonging to the institution) and C.T. SUPURAN (380 Italy)

Edition

51st Conference Synthesis and Analysis of Drugs, 2023

Other information

Language

English

Type of outcome

Prezentace na konferencích

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14160/23:00132044

Organization unit

Faculty of Pharmacy

Keywords in English

triazine; sulfonamide; carbonic anhydrase; inhibitors

Abstract

V originále

Carbonic anhydrases (CA, EC 4.2.1.1) are metalloenzymes catalyzing the reversible hydration of CO2, thereby affecting the pH and related physiological processes in various organisms. In pathogenic bacteria, CAs play an essential role in survival and growth. Inhibition of bacterial CAs leads to growth retardation, growth defects and makes bacteria vulnerable to host defense mechanisms. Bacterial CAs are, therefore, very promising targets in the search for new antibiotics. In humans, 15 different isoforms of CAs can be found, including two tumor-associated (hCA IX, hCA XII). Given the above, it is clear that carbonic anhydrase inhibitors can be drugs for a whole range of diseases. However, a fundamental problem is their selectivity towards a specific isoenzyme. A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs were synthesized as potential CAs inhibitors. The compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. To evaluate the selectivity of the compounds against bacterial CAs towards human CAs, the inhibitory activity of compounds against tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II were determined. Tested compounds had only a negligible effect on physiologically important isoenzymes. In conclusion, newly prepared compounds have great potential as antibacterial agents with high activity and, at the same time, with high selectivity for bacterial CA compared to metabolically important hCA isoenzymes (e.g., hCA I, hCA II) found in the human body.

Links

MUNI/G/1002/2021, interní kód MU

Name: Insight into CAIX structure and function and design of selective inhibitors as potential anti-cancer drugs (Acronym: CAIX-target)

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

Citovat

HAVRÁNKOVÁ, Eva, Jozef CSÖLLEI, Karolína ŠELIGOVÁ and C.T. SUPURAN. NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS. In 51st Conference Synthesis and Analysis of Drugs. 2023.

@proceedings{2330497,
   author = {Havránková, Eva and Csöllei, Jozef and Šeligová, Karolína and Supuran, C.T.},
   booktitle = {51st Conference Synthesis and Analysis of Drugs},
   keywords = {triazine; sulfonamide; carbonic anhydrase; inhibitors},
   language = {eng},
   title = {NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS},
   url = {https://sal2023.fpharm.uniba.sk/wp-content/uploads/2023/09/booklet_web.pdf},
   year = {2023}
}

TY  - CONF
ID  - 2330497
AU  - Havránková, Eva - Csöllei, Jozef - Šeligová, Karolína - Supuran, C.T.
PY  - 2023
TI  - NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS
KW  - triazine
KW  - sulfonamide
KW  - carbonic anhydrase
KW  - inhibitors
UR  - https://sal2023.fpharm.uniba.sk/wp-content/uploads/2023/09/booklet_web.pdf
N2  - Carbonic anhydrases (CA, EC 4.2.1.1) are metalloenzymes catalyzing the reversible hydration of CO2, thereby affecting the pH and related physiological processes in various organisms. In pathogenic bacteria, CAs play an essential role in survival and growth. Inhibition of bacterial CAs leads to growth retardation, growth defects and makes bacteria vulnerable to host defense mechanisms. Bacterial CAs are, therefore, very promising targets in the search for new antibiotics. In humans, 15 different isoforms of CAs can be found, including two tumor-associated (hCA IX, hCA XII). Given the above, it is clear that carbonic anhydrase inhibitors can be drugs for a whole range of diseases. However, a fundamental problem is their selectivity towards a specific isoenzyme. A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs were synthesized as potential CAs inhibitors. The compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. To evaluate the selectivity of the compounds against bacterial CAs towards human CAs, the inhibitory activity of compounds against tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II were determined. Tested compounds had only a negligible effect on physiologically important isoenzymes. In conclusion, newly prepared compounds have great potential as antibacterial agents with high activity and, at the same time, with high selectivity for bacterial CA compared to metabolically important hCA isoenzymes (e.g., hCA I, hCA II) found in the human body.
ER  -

HAVRÁNKOVÁ, Eva, Jozef CSÖLLEI, Karolína ŠELIGOVÁ and C.T. SUPURAN. NOVEL 1,3,5-TRIAZINYL AMINOBENZENESULFONAMIDES AS POTENT CARBONIC ANHYDRASE INHIBITORS. In \textit{51st Conference Synthesis and Analysis of Drugs}. 2023.

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