do Carmo Maquiaveli Claudia, da Silva Edson Roberto, Hild de Jesus Barbara, Oliveira Monteiro Caio Eduardo, Rodrigues Navarro Tiago, Pereira Branco Luiz Octavio, Souza Dos Santos Isabela, Figueiredo Reis Nanashara, Portugal Arieli Bernardo, Mendes Wanderley João Luiz, Borges Farias André, Correia Romeiro Nelilma, de Lima Evanoel Crizanto
Laboratório de Farmacologia e Bioquímica (LFBq), Departamento de Medicina Veterinária, Universidade de São Paulo Faculdade de Zootecnia e Engenharia de Alimentos, Av. Duque de Caxias Norte 225, Pirassununga 13635-900, SP, Brazil.
Laboratório de Catálise e Síntese de Substâncias Bioativas, Instituto Multidisciplinar de Química, CM UFRJ-Macaé, Universidade Federal do Rio de Janeiro, Macaé CEP 27971-525, RJ, Brazil.
Pharmaceuticals (Basel). 2023 Aug 9;16(8):1120. doi: 10.3390/ph16081120.
Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. A centenary approach to antimonial-based drugs was first initiated with the synthesis of urea stibamine by Upendranath Brahmachari in 1922. The need for new drug development led to resistance toward antimoniates. New drug development to treat leishmaniasis is urgently needed. In this way, searching for new substances with antileishmanial activity, we synthesized ten anthranyl phenylhydrazide and three quinazolinone derivatives and evaluated them against promastigotes and the intracellular amastigotes of . Three compounds showed good activity against promastigotes 1b, 1d, and 1g, with IC between 1 and 5 μM. These new phenylhydrazides were tested against arginase, but they all failed to inhibit this parasite enzyme, as we have shown in a previous study. To explain the possible mechanism of action, we proposed the enzyme PTR1 as a new target for these compounds based on in silico analysis. In conclusion, the new anthranyl hydrazide derivatives can be a promising scaffold for developing new substances against the protozoa parasite.
利什曼病是一种被忽视的热带疾病，影响着全球数百万人。1922年，Upendranath Brahmachari合成尿素锑胺，首次开启了基于锑剂药物的百年探索之路。对新药研发的需求导致了对锑酸盐产生耐药性。因此，迫切需要研发治疗利什曼病的新药。通过这种方式，为寻找具有抗利什曼原虫活性的新物质，我们合成了十种蒽基苯肼和三种喹唑啉酮衍生物，并对它们针对前鞭毛体和杜氏利什曼原虫细胞内无鞭毛体的活性进行了评估。三种化合物1b、1d和1g对前鞭毛体表现出良好活性，IC50在1至5 μM之间。正如我们之前研究所表明的，这些新型苯肼针对杜氏利什曼原虫精氨酸酶进行了测试，但它们均未能抑制这种寄生虫酶。为解释其可能的作用机制，基于计算机分析，我们提出将酶PTR1作为这些化合物的新靶点。总之，新型蒽基肼衍生物可能是开发抗原生动物寄生虫新物质的一个有前景的框架。
