Novel sulfonamide incorporating piperazine, aminoalcohol and
1,3,5-triazine structural motifs with  carbonic anhydrase I, II
and IX inhibitory action

J 2018

Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action

HAVRÁNKOVÁ, Eva; Jozef CSÖLLEI; Daniela VULLO; Vladimír GARAJ; Pavel PAZDERA et al.

Základní údaje

Originální název

Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action

Autoři

HAVRÁNKOVÁ, Eva ; Jozef CSÖLLEI; Daniela VULLO; Vladimír GARAJ; Pavel PAZDERA a Claudiu T. SUPURAN

Vydání

Bioorganic Chemistry, 2018, 0045-2068

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10401 Organic chemistry

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.926

Kód RIV

RIV/00216224:14310/18:00102164

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1016/j.bioorg.2017.12.034

UT WoS

000428013300004

EID Scopus

2-s2.0-85044657015

Klíčová slova anglicky

Sym-Triazine Benzene sulfonamides; Carbonic anhydrase; Enzyme inhibition; Isoform selectivity;

Změněno: 23. 2. 2021 12:19, Mgr. Hana Hurtová

Anotace

V originále

A new series of s-triazine derivatives incorporating sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide and piperazine or aminoalcohol structural motifs is reported. Molecular docking was exploited to select compounds from virtual combinatorial library for synthesis and subsequent biological evaluation. The compounds were prepared by using step by step nucleophilic substitution of chlorine atoms from cyanuric chloride (2,4,6-trichloro-1,3,5-triazine). The compounds were tested as inhibitors of physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms. Specifically, against the cytosolic hCA I, II and tumor-associated hCA IX. These compounds show appreciable inhibition. hCA I was inhibited with KIs in the range of 8.5–2679.1 nM, hCA II with KIs in the range of 4.8–380.5 nM and hCA IX with KIs in the range of 0.4–307.7 nM. As other similar derivatives, some of the compounds showed good or excellent selectivity ratios for inhibiting hCA IX over hCA II, of 3.5–18.5. 4-[({4-Chloro-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)methyl] benzene sulfonamide demonstrated subnanomolar affinity for hCA IX (0.4 nM) and selectivity (18.50) over the cytosolic isoforms. This series of compounds may be of interest for the development of new, unconventional anticancer drugs targeting hypoxia-induced CA isoforms such as CA IX.

Citovat

HAVRÁNKOVÁ, Eva; Jozef CSÖLLEI; Daniela VULLO; Vladimír GARAJ; Pavel PAZDERA a Claudiu T. SUPURAN. Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action. Bioorganic Chemistry. 2018, roč. 77, č. 1, s. 25-37. ISSN 0045-2068. Dostupné z: https://doi.org/10.1016/j.bioorg.2017.12.034.

@article{1401799,
   author = {Havránková, Eva and Csöllei, Jozef and Vullo, Daniela and Garaj, Vladimír and Pazdera, Pavel and Supuran, Claudiu T.},
   article_number = {1},
   doi = {https://doi.org/10.1016/j.bioorg.2017.12.034},
   keywords = {Sym-Triazine Benzene sulfonamides; Carbonic anhydrase; Enzyme inhibition; Isoform selectivity;},
   language = {eng},
   issn = {0045-2068},
   journal = {Bioorganic Chemistry},
   title = {Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action},
   url = {https://doi.org/10.1016/j.bioorg.2017.12.034},
   volume = {77},
   year = {2018}
}

TY  - JOUR
ID  - 1401799
AU  - Havránková, Eva - Csöllei, Jozef - Vullo, Daniela - Garaj, Vladimír - Pazdera, Pavel - Supuran, Claudiu T.
PY  - 2018
TI  - Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action
JF  - Bioorganic Chemistry
VL  - 77
IS  - 1
SP  - 25-37
EP  - 25-37
SN  - 00452068
KW  - Sym-Triazine Benzene sulfonamides
KW  - Carbonic anhydrase
KW  - Enzyme inhibition
KW  - Isoform selectivity;
UR  - https://doi.org/10.1016/j.bioorg.2017.12.034
L2  - https://doi.org/10.1016/j.bioorg.2017.12.034
N2  - A new series of s-triazine derivatives incorporating sulfanilamide, homosulfanilamide, 4-aminoethylbenzenesulfonamide and piperazine or aminoalcohol structural motifs is reported. Molecular docking was exploited to select compounds from virtual combinatorial library for synthesis and subsequent biological evaluation. The compounds were prepared by using step by step nucleophilic substitution of chlorine atoms from cyanuric chloride (2,4,6-trichloro-1,3,5-triazine). The compounds were tested as inhibitors of physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms. Specifically, against the cytosolic hCA I, II and tumor-associated hCA IX. These compounds show appreciable inhibition. hCA I was inhibited with KIs in the range of 8.5–2679.1 nM, hCA II with KIs in the range of 4.8–380.5 nM and hCA IX with KIs in the range of 0.4–307.7 nM. As other similar derivatives, some of the compounds showed good or excellent selectivity ratios for inhibiting hCA IX over hCA II, of 3.5–18.5. 4-[({4-Chloro-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)methyl] benzene sulfonamide demonstrated subnanomolar affinity for hCA IX (0.4 nM) and selectivity (18.50) over the cytosolic isoforms. This series of compounds may be of interest for the development of new, unconventional anticancer drugs targeting hypoxia-induced CA isoforms such as CA IX.
ER  -

HAVRÁNKOVÁ, Eva; Jozef CSÖLLEI; Daniela VULLO; Vladimír GARAJ; Pavel PAZDERA a Claudiu T. SUPURAN. Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action. \textit{Bioorganic Chemistry}. 2018, roč.~77, č.~1, s.~25-37. ISSN~0045-2068. Dostupné z: https://doi.org/10.1016/j.bioorg.2017.12.034.

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