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Recently, our group has evaluated the antifungal activity of 8-hydroxyquinonline-5-sulfonic acid (MIC values: 1-512 μg/mL). The purpose of this study was to synthesize novel 8-hydroxyquinoline-5-sulfonamide derivatives and to evaluate their antifungal activity in order to highlight their potential as promising candidates for treatment of fungal infections. The derivatives were synthesized in two steps (10-23% overall yield). The MIC values of compounds ranged from 1 to 64 μg/mL for Candida spp. and dermatophytes. Two compounds were selected for additional studies of toxicity, irritability and PK/PD modeling: PH151 and PH153. PH151, the most potent compound, presented low toxicity in normal cells. The EC50 values obtained by combination of time-kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non-irritant molecules with the absence of topical toxicity. Thus, PH151 and PH153 are promising candidates for treatment of dermatomycosis and candidiasis.
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