A new acridone with antifungal properties againstCandidaspp. and dermatophytes, and antibiofilm activity againstC. albicans

Abstract

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 7Á81-31Á25 µg ml À1 . 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.

Antibiofilm and antifungal activities of medium‐chain fatty acids against Candida albicans via mimicking of the quorum‐sensing molecule farnesol

“…Candida albicans is found in mucosal surfaces and in the gastrointestinal and genitourinary tracts and is the most common cause of systemic and invasive infections. The fungus easily colonizes host tissues and indwelling medical devices (Ramage et al ., 2005), such as urinary catheters, dental materials, artificial heart valves, joint prostheses, penile implants and intrauterine devices (Sardi et al ., 2013; de Oliveira et al ., 2019; Handorf et al ., 2019). Furthermore, biofilms are often tolerant to conventional antifungal therapeutics and the host immune system (Nobile et al ., 2006).…”

‘Acridines’ as New Horizons in Antifungal Treatment

“…Microscopic evaluation of C. albicans hyphal growth in the presence of M14 revealed that the yeast-to-mycelia transformation was completely inhibited. Similarly, severe inhibition of hyphal growth of Trichophyton rubrum was shown [16].…”

“…Recent studies have allowed researchers to obtain a selective derivative M14 ( Figure 2D) with anticandidal and anti-dermatophyte activity and low toxicity to human fibroblasts [16]. M14 exhibited growth-inhibitory activity against all reference and clinical strains of Candida and dermatophytes (MIC range 7.81-31.25 μg mL -1 ).…”

Appraisal of Cinnamaldehyde Analogs as Dual-Acting Antibiofilm and Anthelmintic Agents

“…A report published in 2019 by the Centers for Disease Control and Prevention ( CDC, 2019 ) stated that Candida albicans presents a serious threat via the spread of life-threatening candidiasis ( Ostrosky-Zeichner et al, 2010 ; CDC, 2019 ). C. albicans and its biofilms are found on mucosal surfaces and in the gastrointestinal and genitourinary tracts, and C. albicans readily colonizes host tissues and indwelling medical devices such as urinary catheters, dental implants, artificial heart valves, joint prosthetics, penile implants, and intrauterine devices ( Ramage et al, 2005 ; Sardi et al, 2013 ; De Oliveira et al, 2019 ; Handorf et al, 2019 ). Highly structured C. albicans biofilms form on implant surfaces and subsequently the pathogen disseminate into blood to cause invasive candidiasis, which is responsible for an estimated 100,000 deaths per annum in the United States and for the replacement of over five million central nervous catheters ( Sardi et al, 2013 ).…”