Evaluation of the In Vitro Antifungal Activity of Novel Arylsulfonamides against spp.

The antifungal activity of molecules belonging to the arylsulfonamide chemotype has previously been demonstrated. Here, we screened arylsulfonamide-type compounds against a range of spp. and further established the structure-activity relationship based on a "hit compound". A series of four sulfonamide-based compounds, N-(4-sulfamoylbenzyl) biphenyl-4-carboxamide (), 2,2-diphenyl-N-(4-sulfamoylbenzyl) acetamide (), N-(4-sulfamoylphenethyl) biphenyl-4-carboxamide () and 2,2-diphenyl-N-(4-sulfamoylphenethyl) acetamide (), were tested against the American Type Culture Collection (ATCC) and clinical strains of , and . Based on the fungistatic potential of prototype , a further subset of compounds, structurally related to hit compound , was synthesized and tested: two benzamides (-), the related amine 4-[[(4-4-((biphenyl-4-ylmethylamino)methyl) benzenesulfonamide () and the corresponding hydrochloride, . Both amine and its hydrochloride salt had fungicidal effects against strain 33 (MFC of 1.000 mg/mL). An indifferent effect was detected in the association of the compounds with amphotericin B and fluconazole. The cytotoxicity of the active compounds was also evaluated. This data could be useful to develop novel therapeutics for topical use against fungal infections.