Synthesis and biological investigation of new carbonic anhydrase IX (CAIX) inhibitors.
Chem Biol Interact
; 284: 12-23, 2018 Mar 25.
Article
de En
| MEDLINE
| ID: mdl-29454615
ABSTRACT
In this report, we describe the synthesis, characterization, in vitro anticancer activity and Carbonic anhydrase IX (CAIX) inhibition of new sulfamate conjugates of Betulin and Betulinic acid (BA). The betulinyl sulfamates were subjected to inhibit carbonic anhydrases (CA), e.g. CAIX, an attractive target for tumor-selective therapy strategies in cancer cells. Data on combined in vitro antitumor activity with CAIX inhibition are very rare. The betulinyl sulfamates were tested against five tumor cell lines and normal human skin fibroblasts. The mode of cell death on MCF7 breast cancer cells induced by the most active compounds CAI1, CAI3 and CAI6 was investigated by Fluorescence Activated Cell Sorting (FACS) experiments. The compounds showed inhibitory activity towards CAIX, which was determined via in vitro enz-yme assay. Our preliminary investigations revealed that all compounds showed potent anticancer properties with IC50 values below 20⯵M against all tumor cells. Interestingly, among the panel of sulfamate conjugates, CAI3 found to be highly cytotoxic (average IC50â¯=â¯5-10⯵M) and possess high inhibitory activity (Kiâ¯=â¯1.25â¯nM) towards CAIX. Our results suggest that betulinyl sulfamates seem to be attractive substances, due to their possibility of targeted drug delivery they deserve to be proceeded for further pre-clinical (kinetic studies) and in vivo investigations.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Inhibiteurs de l'anhydrase carbonique
/
Carbonic anhydrase IX
Limites:
Humans
Langue:
En
Journal:
Chem Biol Interact
Année:
2018
Type de document:
Article
Pays d'affiliation:
Allemagne