Santos Gabriela B, Krogh Renata, Magalhaes Luma G, Andricopulo Adriano D, Pupo Mônica T, Emery Flavio S
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
Laboratório de Química Medicinal e Computacional, Universidade de São Paulo, 13560-590 São Carlos, SP, Brazil.
Bioorg Med Chem Lett. 2016 Feb 15;26(4):1205-8. doi: 10.1016/j.bmcl.2016.01.033. Epub 2016 Jan 14.
Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment.
恰加斯病仍然是一种难以根除的疾病，这主要是因为它影响的人群广泛，以及当前治疗方法具有高毒性。因此，迫切需要探索具有理想独特作用机制的创新支架。天然产物阿非迪霉素及其对细胞周期分裂的影响已得到广泛研究；它是一种有效的寄生虫细胞抑制剂。在本研究中，我们首次报道了一系列阿非迪霉素衍生物的半合成、它们独特的结构特征，以及它们对克氏锥虫细胞活性的证明。其中两种对寄生无鞭毛体细胞表现出高效力和选择性，因此有望成为治疗恰加斯病的新先导药物。
