Antifungal Activity of Naphthoquinoidal Compounds In Vitro against Fluconazole-Resistant Strains of Different Candida Species: A Special Emphasis on Mechanisms of Action on Candida tropicalis

Abstract

In recent decades, the incidence of candidemia in tertiary hospitals worldwide has substantially increased. These infections are a major cause of morbidity and mortality; in addition, they prolong hospital stays and raise the costs associated with treatment. Studies have reported a significant increase in infections by non-albicans Candida species, especially C. tropicalis. The number of antifungal drugs on the market is small in comparison to the number of antibacterial agents available. The limited number of treatment options, coupled with the increasing frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. The objective of this study was to evaluate and compare the antifungal activities of three semisynthetic naphthofuranquinone molecules against fluconazole-resistant Candida spp. strains. These results allowed to us to evaluate the antifungal effects of three naphthofuranquinones on fluconazole-resistant C. tropicalis. The toxicity of these compounds was manifested as increased intracellular ROS, which resulted in membrane damage and changes in cell size/granularity, mitochondrial membrane depolarization, and DNA damage (including oxidation and strand breakage). In conclusion, the tested naphthofuranquinones (compounds 1–3) exhibited in vitro cytotoxicity against fluconazole-resistant Candida spp. strains.

Citronellal-induced disruption of membrane homeostasis in Candida albicans and attenuation of its virulence attributes

“…Similarly, retigeric acid B, which is a triterpene acid isolated from Lobaria kurokawa, exerts its antifungal effect against C. albicans through enhanced ROS production (23) . Naphthoquinoidal compounds also exert their effects against Candida species potentially via an increased intracellular ROS production (24) . Therefore, we investigated whether Cit induces oxidative stress in C. albicans.…”

Evaluation of mutagenic and antimicrobial properties of brown propolis essential oil from the Brazilian Cerrado biome

“…Some known antimicrobial agents have been reported to promote DNA damage [34] ⿿including strand breakage as a consequence of oxidative stress, either in mammalian or microbial genomes [35] , [36] , [37] . Although sesquiterpenes are known for their wide range of biological activities, including antimicrobial and antigenotoxic activities, literature reports the induction of DNA damage by sesquiterpene-type compounds with antimicrobial properties [38] , [39] .…”

Antifungal and Antivirulence Activities of Hydroalcoholic Extract and Fractions of Platonia insignis Leaves against Vaginal Isolates of Candida Species

“…Therefore, the treatment of yeast cells with extracts altered the respiratory functions of the mitochondrial membrane and prevented Rho 123 from accumulating in the mitochondrial membrane [26]. The alteration of ∆Ψm can cause a collapse of the membrane and would lead to a transient opening of pores in the membrane, releasing pro-apoptotic factors in the cytosol [27,28]. This, in part, provides a possible explanation for the antifungal potential of the extracts in relation to the number of flavonoid derivatives present in them.…”