新型抗血吸虫药物靶点：通过整合计算机模拟方法鉴定SmTGR的生物碱抑制剂

Novel Antischistosomal Drug Targets: Identification of Alkaloid Inhibitors of SmTGR via Integrated In Silico Methods.

作者信息

Paixão Valéria V M, Santos Yria J A, Fernandes Adriana O, Conceição Elaine S, Rodrigues Ricardo P, Chagas-Paula Daniela A, Dolabella Silvio S, Oliveira Tiago B

机构信息

Posgraduate Program in Chemistry-PPGQ, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil.

Postgraduate Program in Biotechnology-PROBIO, Federal University of Sergipe, Av. Marcelo Deda Chagas, s/n, Bairro Rosa Elze, São Cristóvão 49107-230, SE, Brazil.

出版信息

Pathogens. 2025 Jun 15;14(6):591. doi: 10.3390/pathogens14060591.

DOI:10.3390/pathogens14060591

PMID:40559599

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12196247/

Abstract

Schistosomiasis mansoni is a neglected tropical disease caused by the parasite , affecting approximately 200 million people annually. Currently, treatment relies primarily on a single drug, praziquantel (PZQ), which shows limited efficacy against the parasite's immature forms. As a result, Thioredoxin Glutathione Reductase from (SmTGR) has emerged as a promising target for novel drug development. This study presents the development of integrated in silico methods to identify alkaloids from medicinal plants with potential activity against . Fourteen alkaloids were identified, with predicted activity ranging from 61.3 to 85.2%. Among these, lindoldhamine and daibucarboline A demonstrated, for the first time, potential SmTGR inhibition, with probabilities of 85.2% and 75.8%, respectively. These findings highlight the potential of these alkaloids as promising candidates for the development of new therapies against schistosomiasis.

摘要

曼氏血吸虫病是一种由寄生虫引起的被忽视的热带疾病，每年影响约2亿人。目前，治疗主要依赖单一药物吡喹酮（PZQ），该药物对寄生虫的未成熟形式疗效有限。因此，曼氏血吸虫硫氧还蛋白谷胱甘肽还原酶（SmTGR）已成为新型药物开发的一个有前景的靶点。本研究介绍了整合的计算机模拟方法的开发，以从药用植物中鉴定出对曼氏血吸虫具有潜在活性的生物碱。鉴定出了14种生物碱，预测活性范围为61.3%至85.2%。其中，林多胺和代布卡波林A首次表现出对SmTGR的潜在抑制作用，概率分别为85.2%和75.8%。这些发现突出了这些生物碱作为开发抗血吸虫病新疗法的有前景候选物的潜力。