Synthetic Naphthofuranquinone Derivatives Are Effective in Eliminating Drug-Resistant Candida albicans in Hyphal, Biofilm, and Intracellular Forms: An Application for Skin-Infection Treatment

Abstract

Candida albicans is the most common cause of fungal infection. The emergence of drug resistance leads to the need for novel antifungal agents. We aimed to design naphthofuranquinone analogs to treat drug-resistant C. albicans for topical application on cutaneous candidiasis. The time-killing response, agar diffusion, and live/dead assay of the antifungal activity were estimated against 5-fluorocytosine (5-FC)-or fluconazoleresistant strains. A total of 14 naphthofuranquinones were compared for their antifungal potency. The lead compounds with hydroxyimino (TCH-1140) or O-acetyl oxime (TCH-1142) moieties were the most active agents identified, showing a minimum inhibitory concentration (MIC) of 1.5 and 1.2 µM, respectively. Both compounds were superior to 5-FC and fluconazole for killing planktonic fungi. Naphthofuranquinones efficiently diminished the microbes inside and outside the biofilm. TCH-1140 and TCH-1142 were delivered into C. albicans-infected keratinocytes to eradicate intracellular fungi. The compounds did not reduce the C. albicans burden inside the macrophages, but the naphthofuranquinones promoted the transition of fungi from the virulent hypha form to the yeast form. In the in vivo skin mycosis mouse model, topically applied 5-FC and TCH-1140 reduced the C. albicans load from 1.5 × 10 6 to 5.4 × 10 5 and 1.4 × 10 5 CFU, respectively. The infected abscess diameter was significantly

Four-Arm δ-Ornithine-Based Polypeptoids Resensitize Voriconazole against Azole-Resistant C. albicans

“…The in vivo efficacy of antifungals was examined using a mouse subcutaneous C. albicans infection model. , Immunosuppressed mice (KM, male) were infected by subcutaneous injection of 100 μL 1× 10 9 CFU/mL C. albicans on the back.…”

“…The subcutaneous Candida infection model was conducted by a method similar to a reported protocol. 45 Mice were continuously intraperitoneally injected (i.p.) with cyclophosphamide (100 mg/kg on the first and third days, 150 mg/kg on the second day) to obtain an immunosuppressive mice model.…”

Evaluation of Anti-Candida Potential of Piper nigrum Extract in Inhibiting Growth, Yeast-Hyphal Transition, Virulent Enzymes, and Biofilm Formation

“…Both blastoconidia and hyphae play a crucial role in pathogenesis; however, these display different functions, which include adhesion and invasion [ 82 ]. Several studies have focused on inhibiting these morphological transitions in pathogenic fungi; nevertheless, there is scarce knowledge about the action of natural compounds against this virulence trait in C. albicans [ 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. Some natural and synthetic compounds have been tested and found to be effective in affecting germ tubes or pseudo-hyphae in C. albicans [ 77 , 80 , 84 , 85 ].…”

Effects of 3% Boric Acid Solution on Cutaneous Candida albicans Infection and Microecological Flora Mice

“…The first method is the classical method of directly applying CA solution to the exfoliated epidermis, described by Gaspari ( Santus et al, 2018 ). In this study, we selected the second method of direct intradermal injection discovered by Fang ( Fang et al, 2020 ) to induce the formation of a CA infection model. Five days after inoculation, white membranes, necrosis, erosions, and ulcers appeared on the back of mice.…”