NEW 5-DIMETHYL-3-HETEROARYL-1H-4-ONN-AZOXYCYANIDES: SYNTHESIS AND ANTIMICOTICAL ACTIVITY.

Abstract

In the field of infectious diseases, in the last years an increasingly high importance is ascribed to mycosis as causes of illness and mortality in particularly susceptible patients: leukemia, organ transplant, AIDS and immunosuppressed patients, creating clinical and epidemiological problems. Although several drugs are available, antifungal spectrum is still limited especially for invasive infections, which often have fatal results. We previously reported the antifungal activity of a series of products, in which the 1,5-dimethyl-4-(cyano-NNO-azoxy)pyrazol-3-yl and 1,3-dimethyl-4-(cyano-NNO-azoxy)pyrazol-5-yl moieties were linked to pyridine, pyrazole, isoxazole, thiophene and the furan rings. All compounds displayed interesting antifungal activity against Candida krusei and Candida glabrata, two fungal species resistant to azoles, is noteworthy. The presence of the cyano function appeared essential for activity. The need for novel antifungal agents lead us to synthesize and to investigate the antifungal activity of new ONN-azoxycyano derivatives in which the 3 position is replaced whit quinolinic and bezenic rings. The title compounds tested in vitro for antifungal activity against C. Glabrata and C. Krusei, displayed remarkable antifungal activity, (MIC = 0.25 and 0.5 lg/mL) that means that some of the title compounds were 16 and 32 fold more potent than Amphotericin B and Fluconazole, respectively. These results suggest that, depending on the heterocyclic molecule bound to the 3 position of 1H-4- ONN - azoxycianides, it is possible to modulate the antifungal activity of these new class of derivatives. Synthesis and in vitro biological test of title compounds will be reported.