Synthesis, In Vitro and In Vivo Antifungal Activity of 5-Phenylthio-2,4-Bisbenzyloxypyrimidine: A Novel Nucleobase

A pyrimidne nucleobase, 5-phenylthio-2,4-bisbenzyloxypyrimidine and its analogs were synthesized and scanned for in vitro antifungal activity using cup-plate and macrobroth dilution method against Candida albicans, Aspergillus niger, Aspergillus flavus and Aspergllus fumigatus. In the cup-plate method, 5-phenylthio-2,4-bisbenzyloxypyrimidine showed very good antifungal activity compared to clotrimazole at the concentrations of 100 and 1000 μg/ml and in the macrobroth dilution method, it showed comparable activity with respect to standard drugs fluconazole and itraconaole. In vivo antifungal activity of 5-phenylthio-2,4-bisbenzyloxypyrimidine at the dose levels of 10 and 30 mg/kg was carried by causing systemic infection of mice using the same fungi used in in vitro testing. The results from in vivo studies with 5-phenylthio-2,4-bisbenzyloxypyrimidine and fluconazole indicated that 5-phenylthio-2,4-bisbenzyloxypyrimidine had similar potency as fluconazole at both dose levels.

[1]  Vijayalaxmi Amareshwar.  Facile Route for the Synthesis of Nucleobase Analogs , 2008 .

[2]  F. Odds,et al.  Influences of Methodological Variables on Susceptibility Testing of Caspofungin against Candida Species and Aspergillus fumigatus , 2003, Antimicrobial Agents and Chemotherapy.

[3]  A. Vijayalaxmi,et al.  Antimicrobial activity and structure-activity relationship of acyclic nucleosides , 2003 .

[4]  N. Tsuchimori,et al.  In Vitro and In Vivo Antifungal Activities of TAK-456, a Novel Oral Triazole with a Broad Antifungal Spectrum , 2002, Antimicrobial Agents and Chemotherapy.

[5]  H. Yamaguchi,et al.  In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent , 2002, Antimicrobial Agents and Chemotherapy.

[6]  B. Sharma.  Experiments in microbiology, plant pathology and tissue culture , 1993 .

[7]  K. Chapin,et al.  Effect of medium composition on results of macrobroth dilution antifungal susceptibility testing of yeasts , 1986, Journal of clinical microbiology.

[8]  J. Galgiani,et al.  Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B , 1986, Journal of clinical microbiology.

[9]  J. F. Ryley,et al.  Azole resistance in Candida albicans. , 1984, Sabouraudia.

[10]  D. Stevens,et al.  Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model. , 1983, The Journal of infectious diseases.

[11]  W. Merz,et al.  Incidence of polyene-resistant yeasts recovered from clinical specimens , 1980, Antimicrobial Agents and Chemotherapy.