合成樟脑衍生物(E)-2-((1,7,7-三甲基双环[2.2.1]庚烷-2-酰基)氨基)苯酚:一种新的内脏弓形虫病驱虫药候选药物。

IF 1.6 3区 生物学 Q4 PARASITOLOGY
D C Rodrigues, C N de Oliveira da Cunha, A M Faria, V P Panassolo, L H R Martins, M V N de Souza, M C F D de Souza, L S Munhoz, L F da Costa de Avila, D F Ramos, C J Scaini
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引用次数: 0

摘要

人类弓形虫病是一种全球分布的被忽视的寄生虫病,目前使用的驱虫药疗效低至中等,需要发现新的药物。樟脑衍生物具有抗真菌和细菌等多种病原体的抗菌特性。本研究旨在鉴定一种具有抗犬弓形虫幼虫活性的樟脑衍生物,并评估其在感染该寄生虫的瑞士小鼠体内的细胞毒性、硅生物利用度和活性。三种化合物在1.0 ~ 0.05 mg/mL浓度的条件下,在含有100只犬绦虫幼虫的微孔板上,在rmi -1640培养基中,37℃、5% CO2条件下培养48 h。化合物(E)-2-((1,7,7-三甲基双环[2.2.1]庚烷-2-酰基)氨基)苯酚(C2)的最低杀虫浓度(MLC)为0.25 mg/mL,被选择用于后续步骤。该化合物在MLC中显示出100%的细胞活力,在计算模型中显示出足够的生物利用度。随后对瑞士小鼠进行了两次体内试验,分别在接种后10天(n=5)和30天(n=10)接种500枚犬绦虫感染卵。选择的化合物(10 mg/kg, IG)和两个对照(阿苯达唑,40 mg/kg, IG和磷酸盐缓冲盐水0,15 m, pH 7,2, IG)进行评价。在接种后10天和30天,该化合物分别使感染强度降低了75.7%和54.8% (p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthetic camphor derivative (E)-2-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)amino)phenol: A novel anthelmintic drug candidate for visceral toxocariasis.

Human toxocariasis is a neglected parasitic disease with a global distribution, treated with current anthelmintics that have low to moderate efficacy, and requires the discovery of novel drugs. Camphor derivatives have antimicrobial properties against various pathogens such as fungi and bacteria. This study aimed to identify a camphor derivative with activity against Toxocara canis larvae and evaluate its cytotoxicity, in silico bioavailability, and in vivo activity in Swiss mice infected with this parasite. Three compounds were tested in vitro in duplicate at a concentration of 1.0 to 0.05 mg/mL in a microplate containing 100 T. canis larvae in RPMI-1640 medium incubated for 48 h at 37°C and 5% CO2. The compound (E)-2-((1,7,7-trimethylbicyclo [2.2.1] heptan-2-ylidene)amino)phenol (C2) presented a minimum larvicidal concentration (MLC) of 0.25 mg/mL and was selected for the subsequent steps. This compound showed 100% cell viability in MLC and adequate bioavailability in computational models. Two subsequent in vivo tests were performed on Swiss mice inoculated with 500 T. canis infective eggs through intragastric (IG) intubation, one at 10 days post-inoculation (n=5) and the other at 30 days post-inoculation (n=10). The selected compound (10 mg/kg, via IG) and two controls (albendazole, 40 mg/kg, IG and phosphate buffered saline 0,15M, pH 7,2, via IG) were used for this evaluation. The compound reduced the intensity of infection by 75.7% and 54.8% at 10 and 30 days post inoculation, respectively (p<0.05). The results of this study demonstrate that this compound has potential as an anthelmintic candidate for visceral toxocariasis treatment.

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来源期刊
Journal of Helminthology
Journal of Helminthology 生物-动物学
CiteScore
2.80
自引率
12.50%
发文量
127
审稿时长
3 months
期刊介绍: Journal of Helminthology publishes original papers and review articles on all aspects of pure and applied helminthology, particularly those helminth parasites of environmental health, medical or veterinary importance. Research papers on helminths in wildlife hosts, including plant and insect parasites, are also published along with taxonomic papers contributing to the systematics of a group. The journal will be of interest to academics and researchers involved in the fields of human and veterinary parasitology, public health, microbiology, ecology and biochemistry.
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