In this investigation, researchers produced powerful antifungals of the polyene class without nephrotoxicity.
By Dr. Liji Thomas, MDNov 9 2023Reviewed by Danielle Ellis, B.Sc. Polyenes are among the most commonly used broad-spectrum antifungals but have significant associated renal toxicity. Attempts to develop newer drugs of the same class without these adverse effects led to nothing, mostly because of the perception that their antifungal activity was based on membrane permeabilization.
What did the study show? In a study published in XXX, scientists examined the structure of amphotericin B in its sponge-like state. They observed that it forms a clathrate-like lattice, trapping either ergosterol or cholesterol at a highly conserved region of the polyene macrolide molecule. However, its affinity for ergosterol is higher than for cholesterol.
This new compound is less potent than the parent because of the lower rate of ergosterol extraction, however. The extent of decreased potency varied with the fungal strain, being least for Candida krusei but largest for Aspergillus fumigatus. This indicated that other factors contributed to its potency rather than only ergosterol binding strength.
Related Stories“It is notable that both of these chemical modifications are positioned on the portion of that is conserved in all of the glycosylated polyene macrolide natural products that operate through the same sterol sponge mechanism.”
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