Methods for the Recovery and Purification of Polyene Antifungals

Abstract

Despite the development of newer antifungal drugs, the polyene antifungals continue to be the most potent broad-spectrum fungicides available for clinical use. The incidence and severity of fungal infections are on the rise, underscoring the need for new and more effective antifungal drugs. Thus, the search for new polyene antifungals is ongoing. The limited solubility, polymorphic character, and inherent chemical instability of these compounds make their economical recovery and purification from mass culture challenging problems in biotechnology. This article provides a comprehensive review of the methods that have been developed for the recovery and purification of amphotericin B and nystatin, the two most important polyenes currently in clinical use.

Synthesis and biological evaluation of amphotericin B derivatives

“…Industrial fermentation continues to rely on the fermentation of production strains of S. nodosus. 64,65 Knowledge of the genes for the AmB PKS made it possible to obtain derivatives of AmB and AmA (2) by modification and deletion of specific genes (Fig. 12).…”

The isolation of water-soluble natural products – challenges, strategies and perspectives

“…193 Polyene antifungals are of difficult isolation due to their amphiphilic nature. 194 A new method was devised for the isolation of amphotericin B (27) analogues and of truncated amphotericin B biosynthesis intermediates by the use of XAD-16, which considerably improved the recovery of 27 derivatives from culture media. 195 Membrane ltration and ultraltration are commonly used for macromolecule purication, but rarely employed for small metabolites.…”

“…Such approaches have been successfully utilized over decades, until very recently. A survey on new plant saponins reported in 2020 includes the bufadienolide 191 from Helleborus thibetanus, 617 klaineanoside A (192) from the stem barks of Chytranthus klaineanus, 618 scabioside A (193) from Scabiosa sicula L., 619 trillfurostanoside A (194) from the rhizomes of Trillium tschonoskii 620 and saponin 195 from the roots of Glandularia x hybrida. 621 This journal is © The Royal Society of Chemistry 2022…”

Controlled delivery of membrane proteins to artificial lipid bilayers by nystatin–ergosterol modulated vesicle fusion

“…Nystatin is poorly soluble (4 mg ml À1 in water and 11.2 mg ml À1 in methanol at 28 1C [42]) and chemically unstable; solutions and aqueous suspensions begin to lose antifungal activity soon after preparation [43]. In our experience, reproducible vesicle fusion can only be obtained when the starting material is a fine powder with a pale yellow colour.…”