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

J 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.

Základní údaje

Originální název

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

Autoři

HAVRÁNKOVÁ, Eva (203 Česká republika, garant, domácí), V. GARAJ, S. MASCARETTI, A. ANGELI, Zuzana SOLDÁNOVÁ (203 Česká republika, domácí), M. KEMKA, J. MOTYČKA, Marie BRÁZDOVÁ (203 Česká republika, domácí), Jozef CSÖLLEI (203 Česká republika, domácí), J. JAMPÍLEK a C.T. SUPURAN

Vydání

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2022, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600

Kód RIV

RIV/00216224:14160/22:00125425

Organizační jednotka

Farmaceutická fakulta

DOI

http://dx.doi.org/10.3390/ijms23010231

UT WoS

000751345900001

Klíčová slova anglicky

vancomycin-resistant enterococci; carbonic anhydrase; inhibition; triazine; benzenesulfonamide; stilbene; chalcone

Štítky

rivok, ÚChL, ÚMF

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 2. 2022 14:08, JUDr. Sabina Krejčiříková

Anotace

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.

Návaznosti

MUNI/A/1202/2020, interní kód MU

Název: Syntéza nových potenciálních inhibitorů CA

Investor: Masarykova univerzita, Syntéza nových potenciálních inhibitorů CA

Citovat

HAVRÁNKOVÁ, Eva, V. GARAJ, S. MASCARETTI, A. ANGELI, Zuzana SOLDÁNOVÁ, M. KEMKA, J. MOTYČKA, Marie BRÁZDOVÁ, Jozef CSÖLLEI, J. JAMPÍLEK a 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. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2022, roč. 23, č. 1, s. 1-45. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms23010231.

@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 a 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, roč.~23, č.~1, s.~1-45. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms23010231.

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