用于人类和动物媒介传播寄生虫病的设计良性SAHA类似物。
Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases.
作者信息
Rossi Michele, Martinengo Bianca, Diamanti Eleonora, Salerno Alessandra, Rizzardi Nicola, Fato Romana, Bergamini Christian, Souza de Oliveira Andressa, de Araújo Marques Ferreira Thais, Andrade Holanda Cleonice, Romeiro Luiz Antonio Soares, Soeiro Maria de Nazaré Correia, Nunes Krislayne, Ferreira de Almeida Fiuza Ludmila, Meuser Batista Marcos, Fraga Carlos A M, E A Alkhalaf Hamed, Elmahallawy Ehab Kotb, Ebiloma Godwin U, De Koning Harry P, Vittorio Serena, Vistoli Giulio, Blanquart Christophe, Bertrand Philippe, Bolognesi Maria Laura
机构信息
Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
Laboratório de Desenvolvimento de Inovações Terapêuticas, Núcleo de Medicina Tropical, Faculdade de Medicina, Universidade de Brasília, Brasília 70910-900, Brazil.
出版信息
ACS Med Chem Lett. 2024 Aug 13;15(9):1506-1515. doi: 10.1021/acsmedchemlett.4c00242. eCollection 2024 Sep 12.
The search for new drugs fulfilling One Health and Green Chemistry requirements is an urgent call. Here, for the first time, we envisaged developing SAHA analogues by starting from the cashew nutshell liquid (CNSL) agro-industrial waste and employing a metathesis approach. This sustainable combination (comprising principles #7 and #9) allowed a straightforward synthesis of compounds -. All of them were found to not be toxic on HepG2, IMR-32, and L929 cell lines. Then, their potential against major human and animal vector-borne parasitic diseases (VBPDs) was assessed. Compound emerged as a green hit against the trypomastigote forms of . studies showed that the HDAC (TbDAC) catalytic pocket could be occupied with a similar binding mode by both SAHA and , providing a putative explanation for its antiparasitic mechanism of action (, EC = 0.7 ± 0.2 μM).
寻找符合“同一健康”和绿色化学要求的新药是一项紧迫的任务。在此，我们首次设想从腰果壳液（CNSL）这一农业工业废料出发，采用复分解方法来开发SAHA类似物。这种可持续的组合（包含原则#7和#9）使得能够直接合成化合物-。结果发现，所有这些化合物对HepG2、IMR-32和L929细胞系均无毒性。然后，评估了它们对主要的人类和动物媒介传播寄生虫病（VBPDs）的潜在作用。化合物 成为针对 锥鞭毛体形式的绿色热门化合物。 研究表明，SAHA和 都可以以类似的结合模式占据 组蛋白去乙酰化酶（TbDAC）催化口袋，这为其抗寄生虫作用机制提供了一种假定的解释（，EC = 0.7±0.2 μM）。
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