A new acridone with antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans.

AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.

Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction.

Endothelial dysfunction is a surrogate marker of cardiovascular risk. Resveratrol is known to improve endothelial function in animals, however, clinical trials are limited. We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction. Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a randomized, cross-over, double-blind, placebo-controlled trial. Individuals received either a single dose of trans-resveratrol (300 mg) or placebo and were crossed-over after a one-week washout period. Blood pressure (BP) measurements, aortic systolic blood pressure (SBP) and brachial flow-mediated dilation (FMD) were performed before and 1.5 hours after the intervention. FMD was significantly increased in women (4.2 ± 0.5 vs 7.1 ± 1.3%, p = 0.026) but not in men (4.4 ± 0.9 vs 4.9 ± 0.8%, p = 0.588) in the trans-resveratrol group. There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP. Patients with higher low-density lipoprotein (LDL) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol (7.4 ± 1.2 vs 4.3 ± 1.0%, p = 0.004). Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function, especially in women and those with higher LDL-cholesterol, despite no changes in BP. List of Abbreviation: Aix: augmentation index; AP: augmentation pressure; BP: blood pressure; BMI: body Mass Index; CVD: cardiovascular disease; FMD: flow-mediated dilation; FRS: Framingham Risk Score; HDL: high-density lipoprotein; LDL: low-density lipoprotein; NO: nitric oxide; SPSS: Statistical Package for Social Sciences; ROS: reactive oxygen species; SBP: systolic blood pressure; TG: triglycerides.