A General Overview on Past, Present and Future Antimycotics~!2009-11-01~!2010-04-06~!2010-06-24~!

Abstract

Since the discovery of amphotericin B in 1955 the armamentarium of antimycotic drugs now embraces many new chemical classes: azoles, allylamines and candins. However, despite the wide variety in chemical structure, there is a lack of diversity in terms of mechanism of action. The mechanism of action of the main classes of antimycotics as well as the therapeutic value of some representatives is discussed. Some challenges to innovation will be highlighted that when overcome will herald more effective therapeutic interventions. Finally, we will list antimycotics that are at a late stage of development.

The Need for New Antifungal and Antimalarial Compounds

“…Van Minnebruggen et al [25] concluded that "there is still an unmet medical need to further improve antimycotic therapy and that interdisciplinary research bringing together chemical, molecular and clinical expertise can help make the antimycotic drugs of tomorrow to fulfill the promise of today." One of the approaches could be genome mining of different organisms-actinomycetes and fungi in particular.…”

Imidazolylchromanones containing alkyl side chain as lanosterol 14α-demethylase inhibitors: synthesis, antifungal activity and docking study

“…On the other hand, there are only a few chemotherapeutic agents that can be used for life-threatening fungal infections. Natural products such as polyenes and echinocandins, and synthetic chemicals including flucytosine and azoles are currently available classes of antifungal agents 4 . Among the different classes of antifungal agents that have been discovered, azoles are first-line drugs for the treatment of invasive fungal infections, because of their high therapeutic index.…”

“…The azoles are chemically either an imidazole or a triazole ring attached to a functionalized phenethyl moiety as their pharmacophore ( Figure 1, structure A). Several new azole antifungal agents, such as luliconazole, voriconazole, pramiconazole, posaconazole, albaconazole and isavuconazole are marketed or currently in the late stages of clinical trials 4,5 . However, the extensive use of azoles has led to the development of fungal resistance which significantly reduced their efficacy.…”

Biofilm formation in Malassezia pachydermatis strains isolated from dogs decreases susceptibility to ketoconazole and itraconazole

“…and Coccidioides immitis might also be able to produce fungal biofilms in humans (Cannizzo et al, 2007;Martinez and Fries, 2010). Biofilms are extracellular matrices produced by microorganisms (primarily bacteria and fungi) which help the pathogens attach to viable and non-viable surfaces (Van Minnebruggen et al, 2010). Biofilm formation in Candida albicans resulted in a 30-to 2000-fold decrease in sensitivity to certain antifungals including ketoconazole (Martinez and Fries, 2010;Vandeputte et al, 2012).…”