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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14160%2F23%3A00132044" target="_blank" >RIV/00216224:14160/23:00132044 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů