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靶向蝶呤还原酶 1 和二氢叶酸还原酶:旧的方法成为利什曼病药物发现的新趋势。

Targeting pteridine reductase 1 and dihydrofolate reductase: the old is a new trend for leishmaniasis drug discovery.

机构信息

Laboratório de Síntese Orgânica Medicinal (LaSOM), Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre/RS, Brazil.

出版信息

Future Med Chem. 2019 Aug;11(16):2107-2130. doi: 10.4155/fmc-2018-0512. Epub 2019 Aug 2.

Abstract

Leishmaniasis is one of the major neglected tropical diseases in the world and it is considered endemic in 88 countries. This disease is transmitted by a spp. infected sandfly and it may lead to cutaneous or systemic manifestations. The preconized treatment has low efficacy and there are cases of resistance to some drugs. Therefore, the search for new efficient molecular targets that can lead to the preparation of new drugs must be pursued. This review aims to evaluate both enzymes PTR1 and DHFR-TS as potential drug targets, highlight their inhibitors and to discuss critically the use of chemoinformatics to elucidate interactions and propose new molecules against these enzymes.

摘要

利什曼病是世界上主要的被忽视热带病之一,被认为在 88 个国家流行。这种疾病由感染的沙蝇传播,并可能导致皮肤或全身表现。推荐的治疗方法疗效低,并且存在对某些药物的耐药性。因此,必须继续寻找新的有效分子靶标,以制备新药。本综述旨在评估 PTR1 和 DHFR-TS 这两种酶作为潜在的药物靶点,强调它们的抑制剂,并批判性地讨论利用化学生物信息学来阐明这些酶的相互作用和提出新的分子。

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