Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Version 1 : Received: 15 March 2022 / Approved: 18 March 2022 / Online: 18 March 2022 (07:04:16 CET)

A peer-reviewed article of this Preprint also exists.

Kane, A.; Carter, D.A. Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox. Pharmaceuticals 2022, 15, 482. Kane, A.; Carter, D.A. Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox. Pharmaceuticals 2022, 15, 482.

Journal reference: Pharmaceuticals 2022, 15, 482
DOI: 10.3390/ph15040482

Abstract

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.

Keywords

Keywords: antifungal; azole; synergy; mycosis; resistance; Candida; dermatophytes; natural products

Subject

LIFE SCIENCES, Microbiology

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