Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São José dos Campos, SP, 12245-000, Brazil.
Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba, Brazil.
Folia Microbiol (Praha). 2023 Dec;68(6):999-1004. doi: 10.1007/s12223-023-01104-5. Epub 2023 Nov 11.
Cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis and cryptococcal meningitis, which conventional treatment involves antifungal drugs such as polyenes, flucytosine, azoles, and their combinations. However, the high cost, toxicity, and increase in fungi resistance to antifungal agents stimulate the search for therapeutic strategies such as drug repurposing and combination therapy. This study evaluated the activity of the antihypertensive verapamil (VEH) alone and combined with amphotericin B (AmB) against C. neoformans. VEH exhibited antifungal activity against C. neoformans with minimum inhibitory concentration and minimum fungicidal concentration of 118 µg per mL. The combination of VEH and AmB exhibited synergism, reducing at least eightfold both drugs' concentrations. Moreover, the combination decreased the size and glucuronoxylomannnan content of C. neoformans capsule. However, no difference was observed in ergosterol levels of C. neoformans after treatment with VEH and AmB in combination. Altogether, VEH in combination with AmB exhibits potential as a candidate as for the development of anti-cryptococcal drug.
新生隐球菌是一种有荚膜的酵母，可引起隐球菌病和隐球菌性脑膜炎，其常规治疗包括使用抗真菌药物，如多烯类、氟胞嘧啶、唑类及其联合用药。然而，抗真菌药物治疗费用高、毒性大、真菌耐药性增加，这刺激了人们寻找治疗策略，如药物再利用和联合治疗。本研究评估了单独使用和与两性霉素 B（AmB）联合使用的降压药维拉帕米（VEH）对新生隐球菌的活性。VEH 对新生隐球菌具有抗真菌活性，最低抑菌浓度和最低杀菌浓度均为 118µg/mL。VEH 和 AmB 的联合使用表现出协同作用，使两种药物的浓度至少降低了八倍。此外，该联合用药还降低了新生隐球菌荚膜的大小和葡聚糖甘露聚糖的含量。然而，在用 VEH 和 AmB 联合治疗后，新生隐球菌中的麦角固醇水平没有差异。总之，VEH 与 AmB 联合具有作为抗隐球菌药物开发的候选药物的潜力。
