Synthesis of Some 4-Phenyl/Cyclohexyl-5-(L-Phenoxyethyl)-3-[(3,5-Diaryl-2-Pyrazolinyl)Acetyl]Thio-4h-L,2,4-Triazole Derivatives and their Antifungal Activity

Abstract

Triazol türevleri, azol antifungallerin en büyük kimyasal grubudur. Günümüzde flukonazol ve itrakonazol en sık kullanılan triazol türevleridir. Diğer antifungaller ile kıyaslandığında, düşük toksisite ve geniş etki spektrumuna sahiptirler. Bu çalışmada, yeni antifungal bileşikler olarak 1,2,4-triazol türevlerini sentezlemeyi amaçladık. Alkali siklizasyonla merkaptotrizolleri oluşturan tiyosemikarbazidleri, propiyonik asid hidrazidi ile aril/alkil izotiyosiyanatların reaksiyonu 31 verdi. Merkaptotriazoller ile 1-(2-kloroasetil)-3,5-diaril-2-pirazolinin reaksiyonu ile 4-fenil/siklohegzil-5-(1-fenoksietill)-3-[(3,5-diaril-2-pirazolin-1-il)asetil]tiyo-4H-1,2,4-triazol türevleri sentezlendi. Bileşiklerin kimyasal yapıları ve saflık tayinleri IR, 1H-NMR, FAB-MS spectral verileri ve elemental analiz ile aydınlatıldı. Bileşiklerin antifungal aktiviteleri Candida albicans (2 suş), Candida glabrata, Candida tropicali, Candida krusei , Candida utilis, Geotrichum candidum’a karşı araştırıldı. Sonuçlar, bazı bileşiklerin güçlü antifungal etkiye sahip olduklarını gösterdi.

Triazole derivatives are the major chemical group of antifungal azole derivatives. Nowadays, the most frequently used triazoles are fluconazole and itraconazole. They posses a broad spectrum of antifungal activity and reduced toxicity when compared with the other antifungals. In this study, we aimed the synthesis of new 1,2,4-triazole derivatives as novel antifungal agents. The reaction of propionic acid hydrazides with various aryl/alkyl isothiocyanates gave thiosemicarbazides which furnished the mercaptotriazoles by alkali cyclization. The 4-phenyl/cyclohexyl-5-(l-phenoxyethyl)-3-[(3,5-diaryl-2-pyrazolin-l-yl)acetyl]thio-4H-l,2,4-triazole derivatives were synthesized by reacting the mercaptotriazoles with l-(2-chloroacetyl)-3,5-diaryl-2-pyrazoline. The chemical structures of the compounds were elucidated by IR, 'H-NMR, FAB-MS spectral data and elemental analysis. Their antifungal activities against Candida albicans (two strains), Candida glabrata, Candida tropicalis, Candida krusei , Candida utilis, Geotrichum candidum were investigated. The results showed that some of the compounds have strong antifungal activity.