Alsulaimany Marwa, Binjubair Faizah A, Tatar Esra, Kelly Diane E, Kelly Steven L, Warrilow Andrew G, Keniya Mikhail V, Monk Brian C, Parker Josie E, Simons Claire
School of Pharmacy and Pharmaceutical Sciences, Cardiff University King Edward VII Avenue Cardiff CF10 3NB UK
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University 34668 Istanbul Turkey.
RSC Med Chem. 2025 Mar 12;16(5):2270-2280. doi: 10.1039/d4md00863d. eCollection 2025 May 22.
Fungal infections have been described as a silent crisis affecting more than one billion people each year. At least 150 million of these cases involve severe and life threatening invasive fungal infections, accounting for approximately 1.7 million deaths annually. 1,2,4-Trizoles such as fluconazole and posaconazole are widely used antifungal agents, but azole resistance is an increasing problem requiring further study. 1,2,4-Triazole derivatives with medium and long arm extensions designed to bind within the CYP51 (CaCYP51) access channel were synthesised to study their inhibition of CaCYP51 (IC, MIC) and binding affinity ( ). A long arm extension using the amide linker was found to be most effective (13), giving an antifungal profile wild-type and resistant model fungal strains comparable with posaconazole.
真菌感染已被描述为一场无声的危机，每年影响着超过10亿人。其中至少1.5亿例涉及严重且危及生命的侵袭性真菌感染，每年导致约170万人死亡。氟康唑和泊沙康唑等1,2,4-三唑类药物是广泛使用的抗真菌剂，但唑类耐药性问题日益严重，需要进一步研究。合成了具有中长臂延伸结构、旨在结合CYP51（白色念珠菌CYP51）通道内的1,2,4-三唑衍生物，以研究它们对白色念珠菌CYP51的抑制作用（IC50、MIC）和结合亲和力（ ）。发现使用酰胺连接体的长臂延伸最为有效（13），其对野生型和耐药模型真菌菌株的抗真菌谱与泊沙康唑相当。
