We have reported that 4-nitrosopyrazoles derivatives displayed in vitro potent antifungal activity at no cytotoxic concentrations and that some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus neoformans. We reported also that the absence of NO group or its replacement with NO2 or NH2 groups gave compounds devoid of antimycotical activity.[1,2] With the final aim to gain a deeper insight into the mechanism of action, we studied the in vivo metabolism of some 4-nitrosopyrazoles in rat liver and a rapid metabolization, with formation of the corresponding amines, was observed. [3] These findings and need for novel antifungal agents lead us to synthesize and to investigate the antifungal activity of title compounds in which the 4-NO group was replaced with 4-ONN-azoxycyano group, which having differnt steric and electronic features, may be metabolised in vivo by different routes . Some of synthesized compouds showed interesting in vitro antifungal and antibacterial activity. Synthesis and in vitro bilogical test of title compounds will be reported.
Synthesis and Antimicrobial Activity of New 1,5-Dimethyl-3-Heteroaryl-1H-4-ONN-Azoxycyanides
BOSCHI, Donatella;
2008-01-01
Abstract
We have reported that 4-nitrosopyrazoles derivatives displayed in vitro potent antifungal activity at no cytotoxic concentrations and that some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus neoformans. We reported also that the absence of NO group or its replacement with NO2 or NH2 groups gave compounds devoid of antimycotical activity.[1,2] With the final aim to gain a deeper insight into the mechanism of action, we studied the in vivo metabolism of some 4-nitrosopyrazoles in rat liver and a rapid metabolization, with formation of the corresponding amines, was observed. [3] These findings and need for novel antifungal agents lead us to synthesize and to investigate the antifungal activity of title compounds in which the 4-NO group was replaced with 4-ONN-azoxycyano group, which having differnt steric and electronic features, may be metabolised in vivo by different routes . Some of synthesized compouds showed interesting in vitro antifungal and antibacterial activity. Synthesis and in vitro bilogical test of title compounds will be reported.
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