Design of conformationally constrained azole antifungals: efficient synthesis and antifungal activity of trans-3-imidazolylflavanones.
An efficient protocol has been developed for the preparation of a series of trans-3-imidazolylflavanones and (Z)-trans-3-imidazolylflavanone oximes, as potential antifungal agents, by the reaction of 2-imidazolyl-2'-hydroxyacetophenone with different benzaldehyde derivatives and subsequence oximation reaction. The stereochemical and conformational aspects of compounds were also assigned by (1)H NMR spectroscopy. The aryl group present at C-2 and the imidazole ring present at C-3 were assigned to occupy equatorial position in trans-3-imidazolylflavanones 3 and axial position in (Z)-trans-3-imidazolylflavanone oximes 4. Most of the 3-imidazolylflavanone derivatives containing a substituent on phenyl ring showed significant antifungal activity and modification of the 4-oxo group to oxime or substituent on phenyl ring produced changes in the antifungal activity profile of these compounds. Generally, 3'-chloro- analog of 3-imidazolylflavanone 3c exhibited better profile of antifungal activity against strains of fungi tested, superior than reference drug fluconazole.
Emami
Saeed
S
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. sd_emami@yahoo.com
Behdad
Mehran
M
Foroumadi
Alireza
A
Falahati
Mehraban
M
Lotfali
Ensieh
E
Sharifynia
Somaye
S
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects / Q000254:growth & development; D044950:Flavanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008864:Microsporum / Q000187:drug effects / Q000254:growth & development; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D015003:Yeasts / Q000187:drug effects / Q000254:growth & development
D000935:Antifungal Agents; D044950:Flavanones; D007093:Imidazoles; D010091:Oximes