Coumarin and Piperazine Conjugates as Selective Inhibitors of the Tumor-associated Carbonic Anhydrase IX and XII Isoforms.
Coumarin
carbonic anhydrase
isoform selectivity
modeling
molecular docking
piperazine
synthesis
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2023
2023
Historique:
received:
10
09
2022
revised:
02
12
2022
accepted:
08
12
2022
medline:
6
6
2023
pubmed:
4
2
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
Carbonic Anhydrases (CAs) are a family of metalloenzymes that catalyze the reversible interconversion of CO The objective of this study is to synthesize potent and selective tumor-associated CA IX and XII inhibitors. A library of 17 coumarin derivatives clubbed with piperazine and benzyl moiety was designed, synthesized and evaluated for its inhibitory effects and selectivity profile towards physiologically and pharmacologically relevant CA isoforms I, II, IX, and XII. All the derivatives were found to be active against the tumor-associated isoforms IX and XII. The most active compound against hCA (human Carbonic Anhydrase) IX was found to possess a K Coumarin-piperazine hybrids were identified as potent and selective CA IX and XII inhibitors. Molecular modeling techniques provided interesting cues pertaining to observed selectivity.
Sections du résumé
BACKGROUND
Carbonic Anhydrases (CAs) are a family of metalloenzymes that catalyze the reversible interconversion of CO
OBJECTIVE
The objective of this study is to synthesize potent and selective tumor-associated CA IX and XII inhibitors.
METHODS
A library of 17 coumarin derivatives clubbed with piperazine and benzyl moiety was designed, synthesized and evaluated for its inhibitory effects and selectivity profile towards physiologically and pharmacologically relevant CA isoforms I, II, IX, and XII.
RESULTS
All the derivatives were found to be active against the tumor-associated isoforms IX and XII. The most active compound against hCA (human Carbonic Anhydrase) IX was found to possess a K
CONCLUSION
Coumarin-piperazine hybrids were identified as potent and selective CA IX and XII inhibitors. Molecular modeling techniques provided interesting cues pertaining to observed selectivity.
Identifiants
pubmed: 36733240
pii: ACAMC-EPUB-129240
doi: 10.2174/1871520623666230202123535
doi:
Substances chimiques
Carbonic Anhydrase IX
EC 4.2.1.1
Carbonic Anhydrase Inhibitors
0
Isoenzymes
0
Antigens, Neoplasm
0
Coumarins
0
Piperazines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1184-1191Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.