The antifungal activity of 2,2 '-diamino-4,4 '-dithiazole derivatives is due to the possible inhibition of lanosterol-14-alpha-demethylase

Aryl/alkyl sulfonylamido-, arylsulfenylamido-, arylcarboxamido- and ureido/ thioureido/guanidine derivatives of 2,2'-diamino-4,4'-dithiazole were prepa red by reaction of the title compound with sulfonyl/sulfenyl halides, sulfo nic acid anhydrides, acyl chlorides, tosyl isocyanate, aryl/allyl isocyanat es or isothiocyanates. Mono- as well as bis-derivatized compounds have been obtained. Several of the newly synthesized compounds act as effective anti fungal agents against Aspergillus and Candida spp., some of them showed act ivities comparable to ketoconazole (with minimum inhibitory concentrations in the range of 0.2-1.8 mu g/mL) but possessed lower activity as compared t o itraconazole. Greatest activity was detected against A. niger, and least activity against C. albicans. The mechanism of action of these compounds pr obably involves inhibition of ergosterol biosynthesis, and interaction with lanosterol-14-alpha-demethylase (CYP51Al), since reduced amounts of ergost erol were found by means of HPLC in cultures of the sensitive strain A. nig er treated with some of these inhibitors. Thus, the compounds reported here and the azole antifungal derivatives might possess a similar mechanism of action at molecular level.