Jump to main content
Jump to site search

Issue 6, 2012
Previous Article Next Article

Synthesis and biological evaluation of imidazolylmethylacridones as cytochrome P-450 enzymes inhibitors

Author affiliations

Abstract

Two positional isomers with the general formula 1H-imidazol-1-ylmethylacridin-9(10H)-one were synthesized (5, 6) and evaluated for their inhibitory activity versus CYP11B1, CYP11B2, CYP17 and CYP19. Compound 5 was more effective than letrozole in inhibiting CYP19 (aromatase). Interestingly, compound 5 also inhibited CYP11B1 with an IC50 of 21.2 nM. On the other hand compound 6 was almost completely inactive against all CYPs; this indicates that the positioning and spatial orientation of the imidazolylmethyl moiety is of paramount importance to activity. Sequence alignment of the four steroidogenic CYP enzymes and docking studies with 5, 6 and letrozole supported this finding and suggested Ser478 to be an essential residue for both inhibition and selectivity. These novel compounds may have benefits for the treatment of Cushing's syndrome, hypertension, congestive heart failure and myocardial fibrosis and breast cancer.

Graphical abstract: Synthesis and biological evaluation of imidazolylmethylacridones as cytochrome P-450 enzymes inhibitors

Back to tab navigation

Supplementary files

Article information


Submitted
16 Mar 2012
Accepted
10 Apr 2012
First published
16 Apr 2012

Med. Chem. Commun., 2012,3, 663-666
Article type
Concise Article

Synthesis and biological evaluation of imidazolylmethylacridones as cytochrome P-450 enzymes inhibitors

A. H. Abadi, S. M. Abou-Seri, Q. Hu, M. Negri and R. W. Hartmann, Med. Chem. Commun., 2012, 3, 663
DOI: 10.1039/C2MD20072D

Search articles by author

Spotlight

Advertisements