The antifungal activity of sulfonylamido derivatives of 2- aminophenoxathiin and related compounds

Article abstract of DOI:10.1016/S0223-5234(99)80034-8

Aryl/alkyl-sulfonylamido, arylsulfenylamido, arylcarboxamido and ureido/thioureido derivatives of 2-aminophenoxathiin were prepared by reaction of the title compound with sulfonyl/sulfenyl halides, sulfonic acid anhydrides, acyl chlorides, tosyl isocyanate, aryl/allyl isocyanates or isothiocyanates. Some of these derivatives, containing free amino groups, have been further derivatized by reaction with 2,4,6-trisubstituted-pyrylium salts, aryl/allyl isocyanate/isothiocyanates or tosyl isocyanate. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole or itraconazole (against the aspergilli) but being much less effective against Candida. The mechanism of action of these compounds involves inhibition of ergosterol biosynthesis, and probably interaction with lanosterol-14-α-demethylase (CYP51A1), since reduced amounts of ergosterol were evidenced by means of HPLC in cultures of the sensitive strain A. niger treated with some of these inhibitors. Thus, the two classes of antifungal compounds, i.e. the azoles and the new derivatives reported here, might possess a similar mechanism of action at molecular level.