Update on fungal lipid biosynthesis inhibitors as antifungal agents

Abstract

Fungal diseases today represent a world-wide problem. Poor hygiene and decreased immunity are the main reasons behind the manifestation of this disease. After COVID-19, an increase in the rate of fungal infection has been observed in different countries. Different classes of antifungal agents, such as polyenes, azoles, echinocandins, and anti-metabolites, as well as their combinations, are currently employed to treat fungal diseases; these drugs are effective but can cause some side effects and toxicities. Therefore, the identification and development of newer antifungal agents is a current need. The fungal cell comprises many lipids, such as ergosterol, phospholipids, and sphingolipids. Ergosterol is a sterol lipid that is only found in fungal cells. Various pathways synthesize all these lipids, and the activities of multiple enzymes govern these pathways. Inhibiting these enzymes will ultimately impede the lipid synthesis pathway, and this phenomenon could be a potential antifungal therapy. This review will discuss various lipid synthesis pathways and multiple antifungal agents identified as having fungal lipid synthesis inhibition activity. This review will identify novel compounds that can inhibit fungal lipid synthesis, permitting researchers to direct further deep pharmacological investigation and help develop drug delivery systems for such compounds.

Keywords: Antifungal agents; Ergosterol; Fungal disease; Lipid biosynthesis inhibitors; Phospholipid; Sphingolipids.