Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F18%3A43877051" target="_blank" >RIV/62157124:16370/18:43877051 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/18:00102164
Result on the web
<a href="http://dx.doi.org/10.1016/j.bioorg.2017.12.034" target="_blank" >http://dx.doi.org/10.1016/j.bioorg.2017.12.034</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2017.12.034" target="_blank" >10.1016/j.bioorg.2017.12.034</a>
Alternative languages
Result language
angličtina
Original language name
Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine structural motifs with carbonic anhydrase I, II and IX inhibitory action
Original language description
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
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Bioorganic Chemistry
ISSN
0045-2068
e-ISSN
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Volume of the periodical
77
Issue of the periodical within the volume
April
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
25-37
UT code for WoS article
000428013300004
EID of the result in the Scopus database
2-s2.0-85044657015