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
Author(s): María Daniela Santi, María Gabriela Ortega and Mariana Andrea Peralta*
Affiliation:
- Farmacognosia, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la torre y Medina Allende, Edificio Ciencias II, X5000HUA Córdoba, Argentina
- Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Ciudad Universitaria. X5000HUA Córdoba, Argentina
Keywords:
Prenyl flavonoids, antifungal multidrug resistance, Candida albicans, ABC transporters, MFS transporters, structure-activity relationship.
Abstract:
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.
