UNASSIGNED: The prevalence of invasive @entity364 worldwide has increased in the last decades. The development of specific drugs targeting pathogenic fungi without producing collateral damage to @entity1 cells is a daunting pharmacological challenge. Indeed, many of the @entity137 and drug interactions observed with contemporary antifungal therapies can be attributed to "nonselective" interactions with enzymes or cell membrane systems found in @entity1 host cells. A computer-aided screening strategy against the TRR1 protein of @entity35651 is presented here. Initially, a bank of commercially available compounds from Life Chemicals provider was docked to model by virtual screening simulations. The small molecules that interact with the model were ranked and, among the best hits, twelve compounds out of 3,000 commercially-available candidates were selected. These molecules were synthesized for validation and in vitro antifungal activity assays for @entity35651 and @entity12267 were performed. From 12 molecules tested, 3 harbor inhibitory activity in antifungal assays against the two pathogenic fungi. Corroborating these findings, the molecules have inhibitory activity against the purified recombinant enzyme TRR1 in biochemical assays. Therefore, a rational combination of molecular modeling simulations and virtual screening of new drugs has provided a cost-effective solution to an early-stage medicinal challenge. These results provide a promising technique to the development of new and innovative drugs.

Identification of New Antifungal Compounds Targeting Thioredoxin Reductase of XXXX Genus.

@entity1 :: ('9606', 'Species') :: ['mammalian'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity12267 :: ('121759', 'Species') :: ['P. brasiliensis'] @entity364 :: ('MESH:D009181', 'Disease') :: ['fungal infections'] @entity35651 :: ('1048829', 'Species') :: ['Paracoccidioides lutzii']
@entity12267 :: (121759,Species) :: ['Paracoccidioides']
