Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives.
Even though there are new classes of compounds now frequently used in treatment of fungal infections, the density of deeply invasive candidiasis has increased at least 10-fold during the past decade. Furthermore, many infections due to Candida species are actually refractory to antifungal therapy. In this present study, it was aimed to synthesize, new hydrazide derivatives of tetrahydroimidazo[1,2-a]pyridine and evaluate their anticandidal activity and cytotoxicity in vitro. The reaction of tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid benzylidene hydrazide derivatives. The chemical structures of the compounds were elucidated and confirmed by IR, 1H NMR, MS-FAB+ spectroscopy and elemental analyses. Eight new tetrahydroimidazo[1,2-a]pyridine derivatives were synthesized and screened for their antifungal effects against a panel of ten human pathogenic Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida utilis, and Candida zeylanoides using agar diffusion and broth microdilution assays, respectively. Furthermore, their cytotoxicity was tested against six mammalian cell lines. Among the analogues, the compound 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid-(4-cyanobenzylidene) showed very strong inhibitory activity (up to MIC 0.016 mg/mL) against the screened Candida species. The same compound showed no in vitro toxicity up to 25 microg/mL concentration suggesting that its antifungal activity (MICs 0.016-1 mg/mL) is selective.
Ozdemir
Ahmet
A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
Turan-Zitouni
Gülhan
G
Asim Kaplancikli
Zafer
Z
Işcan
Gökalp
G
Khan
Shabana
S
Demirci
Fatih
F
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000935:Antifungal Agents; D007093:Imidazoles; D011725:Pyridines