Rodríguez-Villar Karen, Hernández-Campos Alicia, Yépez-Mulia Lilián, Sainz-Espuñes Teresita Del Rosario, Soria-Arteche Olivia, Palacios-Espinosa Juan Francisco, Cortés-Benítez Francisco, Leyte-Lugo Martha, Varela-Petrissans Bárbara, Quintana-Salazar Edgar A, Pérez-Villanueva Jaime
Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana (UAM), Ciudad de México 04960, Mexico.
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, Mexico.
Pharmaceuticals (Basel). 2021 Feb 24;14(3):176. doi: 10.3390/ph14030176.
Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against , , and strains. The series of 3-phenyl-1-indazole moiety () demonstrated to have the best broad anticandidal activity. Particularly, compound , with ,-diethylcarboxamide substituent, was the most active against and both miconazole susceptible and resistant species. Therefore, the 3-phenyl-1-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype.
念珠菌病由念珠菌属酵母菌引起，是浅表和黏膜感染的第二大病因以及血流感染的第四大病因。尽管有一些治疗念珠菌病的抗真菌药物，但对当前疗法产生耐药性的菌株正在出现。因此，寻找新的杀念珠菌化合物无疑是当务之急。在这方面，本研究设计了一系列吲唑和吡唑衍生物，采用生物电子等排体替换、同系化和分子简化作为新型抗念珠菌剂。合成了化合物并针对、和菌株进行了评估。一系列3-苯基-1-吲唑部分（）显示出最佳的广泛抗念珠菌活性。特别是，具有，-二乙基甲酰胺取代基的化合物对咪康唑敏感和耐药的物种以及均最具活性。因此，3-苯基-1-吲唑支架代表了开发具有新化学类型的新型抗念珠菌剂的机会。
