In vitro activity of a novel antifungal compound, MYC-053, against clinically significant antifungal-resistant strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp

Abstract

An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with the minimum inhibitory concentrations (MIC) of 0.125–4.0 μg/mL. Notably, unlike other antifungal compounds, MYC-053 was effective against Pneumocystis isolates. MYC-053 was highly effective against preformed 48-h-old yeast biofilms, with the minimal biofilm eradication concentrations equal to 1–4 times MIC. The compound was not cytotoxic against L2 and A549 cell lines at concentrations over 100 μg/ml. Further, it possessed no apparent hemolytic activity up to 1000 μg/ml (the highest concentration tested). Overall, these data indicated that MYC-053 has a broad therapeutic window and may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi in neutropenic patients.

Small molecules for combating multidrug-resistant superbug Candida auris infections

“…The pyrimidinedione derivative MYC-053 ( 48 ) showed broad spectrum effects against Candida spp., Cryptococcus spp., and Pneumocystis spp. It had an MIC value of 4 μg/mL against 5 C. auris isolates, and it was also active against several strains resistant to fluconazole and caspofungin 151 .…”

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

“…In 2019, Tetz et al described the in vitro activity of a novel compound name 053 ( Figure 13) against clinically significant multidrug resistant strains such as C. C. auris, C. neoformans and Pneumocystis spp. [77,78]. Under their screening con MYC-053 proved to be equally effective against both susceptible control strains, Montoya et al reported that derivatives of the anti-malarial drug mefloquine have broad-spectrum antifungal activity against pathogenic yeasts and molds [80].…”

“…CSA steroids as patented by Genberg, Beus and Savage and MYC-053 as reported byTetz. In 2019, Tetz et al described the in vitro activity of a novel compound named MYC-053 (Figure 13) against clinically significant multidrug resistant strains such as C. glabrata, C. auris, C. neoformans and Pneumocystis spp [77,78]…”

Antifungal Drug Development: Targeting the Fungal Sphingolipid Pathway

“…Because of this, drug resistance of common fungal pathogens, such as C. neoformans , C. albicans , and A. fumigatus , has become a growing burden on the healthcare system worldwide. Most alarming is the emergence of fungal species, such as C. auris and C. glabrata , that were already resistant to current antifungal agents [ 12 ]. Thus, there is an urgency for the development of novel antifungal drugs with new mechanisms of action to be used alone or in combination with current antifungals.…”