Antifungal Phenothiazines: Optimization, Characterization of Mechanism, and Modulation of Neuroreceptor Activity.

ABSTRACT: New classes of antifungal drugs are an urgent unmet clinical need. One approach to the challenge of developing new antifungal drugs is to optimize the antifungal properties of currently used drugs with favorable pharmacologic properties, so-called drug or scaffold repurposing. New therapies for cryptococcal meningitis are particularly important given its worldwide burden of disease and limited therapeutic options. We report the first systematic structure-activity study of the anticryptococcal properties of the phenothiazines. We also show that the antifungal activity of the phenothiazine scaffold correlates well with its calmodulin antagonism properties and, thereby, provides the first insights into the mechanism of its antifungal properties. Guided by this mechanism, we have generated imp

SUBMITTER: Montoya MC 

PROVIDER: S-EPMC8994671 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature