Antifungals discovery: an insight into new strategies to combat antifungal resistance

Abstract

Significance and Impact of the Study: The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds. AbstractUndeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.

Nanoemulsion Improves the Antifungal Activity of Allylic Thiocyanates against Yeasts and Filamentous Pathogenic Fungi

“…Fungal infections produce high rates of morbidity and mortality, especially in severely ill or immunocompromised patients , . Candida albicans is a prominent fungal pathogen in humans.…”

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

“…Noteworthy, the compounds of groups 1 and 2, with emphasis on compound 2j , showed activity against resistant yeast species and a multidrug‐resistant dermatophyte ( T mentagrophytes ; Table ), closely related to difficult‐to‐treat dermatomycoses . Considering the fungal species presented in Table , for Candida spp.…”

“…For Candida spp., in patients of chronic mucocutaneous candidiasis, resistance to ketoconazole was first verified in 1980 and the problem of yeast resistance to azoles continues today, almost 40 years after that first report . Also considering the few options of antifungal drugs available, one of the main strategies for improving the mycoses therapy is overcoming antifungal resistance and all limitations involved in the process . Therefore, the prospection of new drugs and formulations to treat dermatomycosis is needed, to bring advances and insights that facilitate the development of novel strategies for antifungal therapy.…”

“…17 Also considering the few options of antifungal drugs available, one of the main strategies for improving the mycoses therapy is overcoming antifungal resistance and all limitations involved in the process. 21,22 Therefore, the prospection of new drugs and formulations to treat dermatomycosis is needed, to bring advances and insights that facilitate the development of novel strategies for antifungal therapy.…”

Eine strukturelle Evaluierung medizinalchemischer Strategien gegen Wirkstoffresistenzen

“…Gegenwärtig werden fünf Klassen antimykotischer Mittel zur Behandlung von Pilzinfektionen beim Menschen verwendet: [358,359] [360][361][362] wird sich dieser Te il des Aufsatzes auf die grçßte und am meisten untersuchte dieser Klassen, die Azole,k onzentrieren und ihre Wirkungsweise,ihre Widerstandsmechanismen und die gegenwärtigen Entwicklungen hervorheben. …”