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EDBD - 3,6 - 环氧 - 1,10 - 愈创木二烯 - 一种从(林仙科)植物中获得的内过氧化物倍半萜,对(某种感染)显示出强大的临床前疗效。

EDBD-3,6-Epidioxy-1,10-Bisaboladiene-An Endoperoxide Sesquiterpene Obtained from (Winteraceae) Exhibited Potent Preclinical Efficacy against Infection.

作者信息

Umehara Eric, Teixeira Thainá R, Cajás Rayssa A, Amaro Monique C, de Moraes Josué, Lago João Henrique G

机构信息

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André 09280-560, SP, Brazil.

Centro de Pesquisas de Doenças Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, Brazil.

出版信息

Antibiotics (Basel). 2024 Aug 18;13(8):779. doi: 10.3390/antibiotics13080779.

DOI:10.3390/antibiotics13080779
PMID:39200079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11350924/
Abstract

Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against EDBD exhibited a significant reduction in viability in vitro, with an effective concentration (EC) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of -infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel's efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment.

摘要

血吸虫病是一种被忽视的热带病,全球有超过2.5亿人受其影响,因其流行程度以及对受影响社区的重大影响,它仍然是一项重大的公共卫生挑战。吡喹酮是唯一可用的治疗药物,这凸显了迫切需要新型驱虫剂以实现世界卫生组织(WHO)消除血吸虫病目标的必要性。先前的研究报道了不同萜类化合物对血吸虫(双口吸虫目:裂体科)具有有前景的抗寄生虫活性。在本研究中,[植物名称]树枝的己烷提取物得到了一种内过氧化物倍半萜的非对映异构体混合物,包括3,6-环氧-双环[3.2.1]辛-1,10-二烯(EDBD)。该化合物在体外和体内针对[血吸虫名称]进行了评估。EDBD在体外显示出[血吸虫名称]活力的显著降低,有效浓度(EC)值为4.1μM。此外,EDBD对哺乳动物细胞无毒性。计算机模拟分析预测其具有良好的类药性质,符合制药行业标准,包括有利的药代动力学性质。此外,用EDBD(400mg/kg)口服治疗感染[血吸虫名称]的小鼠,导致虫卵负荷显著降低(组织和粪便中的虫卵负荷分别降低98%和99%),超过了吡喹酮的疗效。这些发现表明EDBD作为开发新型血吸虫病治疗药物的先导分子具有有前景的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/9f74e134cfc7/antibiotics-13-00779-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/cb4238b9c337/antibiotics-13-00779-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/4e2a58a27a7e/antibiotics-13-00779-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/a0422cef0242/antibiotics-13-00779-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/cb0d51334926/antibiotics-13-00779-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/9f74e134cfc7/antibiotics-13-00779-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/cb4238b9c337/antibiotics-13-00779-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/4e2a58a27a7e/antibiotics-13-00779-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/a0422cef0242/antibiotics-13-00779-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/cb0d51334926/antibiotics-13-00779-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/11350924/9f74e134cfc7/antibiotics-13-00779-g005.jpg

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