Bąchor Urszula, Brożyna Malwina, Junka Adam, Chmielarz Mateusz Ramires, Gorczyca Damian, Mączyński Marcin
Department of Organic Chemistry and Drug Technology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Unique Application Model Laboratory, Department of Pharmaceutical Microbiology and Parasitology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Int J Mol Sci. 2024 Dec 19;25(24):13618. doi: 10.3390/ijms252413618.
Microbiological communities have a significant impact on health and disease. are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of -based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti- potential. Two compounds, and , displayed selective antifungal activity without negatively affecting beneficial microbiota, such as sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of and against , coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs.
微生物群落对健康和疾病有重大影响。[具体真菌名称]是普遍存在的真菌病原体，可定殖于生殖器、泌尿、呼吸和胃肠道以及口腔的粘膜表面。如果免疫系统不足，那么[具体真菌名称]感染可能构成重大威胁。由于临床上用于治疗基于[具体真菌名称]感染的药物数量有限，且对现有抗真菌药物的耐药性迅速出现，因此合成了一系列新型异恶唑基衍生物，并在体外评估了它们的抗[具体真菌名称]潜力。两种化合物，[化合物名称1]和[化合物名称2]，显示出选择性抗真菌活性，同时不会对有益微生物群（如[具体微生物名称]属）产生负面影响。此外，与传统应用的局部抗菌剂（二盐酸奥替尼啶）相比，这些化合物表现出显著更低的细胞毒性，表明它们在治疗外阴阴道念珠菌病等病症方面具有安全有效的临床应用潜力。[化合物名称1]和[化合物名称2]对[具体真菌名称]的选择性抗真菌活性，加上其无抗菌作用且对HeLa细胞的细胞毒性最小，表明其作用机制具有针对性，值得进一步研究。考虑到寻找新型抗真菌药物的必要性以及发现一种不抑制乳酸杆菌生长的抗真菌潜在药物可能是预防和对抗外阴阴道念珠菌病的潜在策略。这种根除由[具体真菌名称]形成的生物膜的显著能力揭示了一种根除生物膜的新方法，并阐明了异恶唑基衍生物作为有前景的抗生物膜药物的潜力。
