Small molecules for combating multidrug-resistant superbug Candida auris infections

Construction and Evaluation of Novel Dual-function Antifungal Inhibitors and Covalent Organic Framework Carriers Based on the Infection Microenvironment

“…Design of Novel Dual-Target Compounds. Based on the above analysis, these potent fragments (1,4,5,7,8,9) were further introduced to design the novel dual-target compounds. In this process, the biphenyl group (1) was used as the main chain fragment of novel compounds, which exhibited excellent dual-target binding ability in the upper active region.…”

“…6 In particular, the emergence of drug-resistant fungi was becoming more and more frequent, which further exacerbated the difficulty of their treatment. 7,8 Therefore, this was an urgent demand to develop novel antifungal inhibitors with highly effective and safe properties.…”

Antifungal Development and the Urgency of Minimizing the Impact of Fungal Diseases on Public Health

“… 12 , 13 , 20 , 35 , 41 , 42 In this scenario, drugs affecting C. auris growth have been continuously investigated, with considerable progress reported for molecules affecting the fungal mitochondria, plasma membrane, biofilms, and cell wall. 47 , 48 …”

“…Antifungal resistance is now a topic that necessarily includes Candida auris, an emerging fungal pathogen that has gained great importance in recent years due to its intrinsic resistance to antifungals and great ability to spread in the environment, affecting especially immunocompromised patients in the hospital environment. − C. auris was first reported in 2009 at a Japanese hospital and since then, it was associated with disease in more than 30 countries from all continents. ,− In the US, for example, the Centers for Disease Control and Prevention (CDC) reported a significant increase in C. auris infections, from 309 cases in 2013 to 1012 cases in 2018 . The impact of the emergence of C. auris on public health is directly linked to the fact that C. auris can be resistant to azoles, echinocandins, and polyenes. , In fact, multidrug-resistant (MDR) isolates have been frequently reported worldwide, including resistance to two or more classes of antifungals. ,− Some of the C. auris isolates show an alarmingly low susceptibility to amphotericin B. ,,,,, In this scenario, drugs affecting C. auris growth have been continuously investigated, with considerable progress reported for molecules affecting the fungal mitochondria, plasma membrane, biofilms, and cell wall. , …”

“…12,13,20,35,41,42 In this scenario, drugs affecting C. auris growth have been continuously investigated, with considerable progress reported for molecules affecting the fungal mitochondria, plasma membrane, biofilms, and cell wall. 47,48 Antifungal resistance is not only problematic in C. auris. Aspergillus species, in particular A. f umigatus, are mostly responsible for mold infections, affecting mainly immunocompromised patients.…”