Title:A State-of-the-art Review and Prospective Therapeutic Applications
of Prenyl Flavonoids as Chemosensitizers against Antifungal Multidrug
Resistance in Candida albicans
Volume: 29
Issue: 24
关键词:
戊烯基类黄酮，抗真菌多药耐药，白色念珠菌，ABC转运体，MFS转运体，构效关系。
摘要:
Multidrug resistance (MDR) in the opportunistic pathogen Candida albicans
is defined as non-susceptibility to at least one agent in two or more drug classes. This
phenomenon has been increasingly reported since the rise in the incidence of fungal infections
in immunocompromised patients at the end of the last century.
After the discovery of efflux pump overexpression as a principal mechanism causing
MDR in Candida strains, drug discovery targeting fungal efflux transporters has had a
growing impact. Chemosensitization aims to enhance azole intracellular concentrations
through combination therapy with transporter inhibitors. Consequently, the use of drug efflux
inhibitors combined with the antifungal agent will sensitize the pathogen. As a result,
the use of lower drug concentrations will reduce possible adverse effects on the
host.
Through an extensive revision of the literature, this review aims to provide an exhaustive
and critical analysis of the studies carried out in the past two decades regarding the chemosensitization
strategy to cope with multidrug resistance in C. albicans. This work provides
a deep analysis of the research on the inhibition of drug-efflux membrane transporters
by prenylated flavonoids and the interactions of these phytocompounds with
azole antifungals as an approach to chemosensitize multidrug-resistant C. albicans
strains. We highlight the importance of prenylflavonoids and their particular chemical
and pharmacological characteristics that make them excellent candidates with therapeutic
potential as chemosensitizers. Finally, we propose the need for further research on prenyl
flavonoids as inhibitors of drug-efflux mediated fungal resistance.
