Sulfonylamido Derivatives of 2-Aminophenoxathiin-10,10-Dioxide and Related Compounds Possess Antifungal Action Due to the Possible Inhibition of Lanosterol-14-α-Demethylase

Abstract

Aryl/alkyl-sulfonylamido-, arylsulfenylamido-, arylcarboxamido-, and ureido/thioureido derivatives of 2-aminophenoxathiin-10.10-dioxide were prepared by reaction with sulfonyl/sulfenyl halides, sulfonic acid anhydrides, acyl chlorides, tosyl isocyanate, aryl/allyl isocyanates or iso-thiocyanates. Some of these derivatives, containing free amino groups, were 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 ketocona-zole, with minimum inhibitory concentrations in the range of 0.3-0.5 μg/mL. Their mechanism of antifungal action is hypothesized to be due to inhibition of lanosterol-14-α-demethylase.

Key Words:

• 2-Aminophenoxathiin-10,10-dioxide
• Sulfonyl halides
• Iso(thio)cyanates
• (Thio)ureas
• Antifungal compounds
• Lanosterol-14-α-demethylase