3-Methylthiazolo[3,2-a]benzimidazole-benzenesulfonamide conjugates as novel carbonic anhydrase inhibitors endowed with anticancer activity: Design, synthesis, biological and molecular modeling studies.
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Benzimidazoles
/ chemical synthesis
Carbonic Anhydrase Inhibitors
/ chemical synthesis
Carbonic Anhydrases
/ chemistry
Catalytic Domain
Cell Cycle
/ drug effects
Cell Proliferation
/ drug effects
Drug Design
Humans
Isoenzymes
/ antagonists & inhibitors
MCF-7 Cells
Models, Molecular
Sulfonamides
/ chemistry
Benzenesulfonamides
Anticancer agents
Carbonic anhydrase inhibitors
Molecular modeling
SLC-0111 analogues
Tail approach
thiazolo[3,2-a]benzimidazole
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
03
07
2020
revised:
30
07
2020
accepted:
31
07
2020
pubmed:
3
9
2020
medline:
20
4
2021
entrez:
3
9
2020
Statut:
ppublish
Résumé
Herein we describe design and synthesis of different series of novel small molecules featuring 3-methylthiazolo[3,2-a]benzimidazole moiety (as a tail) connected to the zinc anchoring benzenesulfonamide moiety via ureido (7), enaminone (12), hydrazone (14), or hydrazide (15) linkers. The newly prepared conjugates have been screened for their inhibitory activities toward four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms: hCA I, II, IX and XII. Thereafter, the urea and enaminone linkers were elongated by one- or two-atoms spacers to afford the elongated counterparts 9 and 13, respectively. Finally, the zinc anchoring sulfonamide group was replaced by the carboxylic acid group to afford acids 17. Compounds 12d, 13b and 15 displayed single-digit nanomolar CA IX inhibitory activities (K
Identifiants
pubmed: 32877804
pii: S0223-5234(20)30717-0
doi: 10.1016/j.ejmech.2020.112745
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Benzimidazoles
0
Carbonic Anhydrase Inhibitors
0
Isoenzymes
0
Sulfonamides
0
benzimidazole
E24GX49LD8
Carbonic Anhydrases
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112745Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.