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10-羟基软骨素和tafenoquine对(HTD)的疗效评估。

Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against (HTD).

作者信息

Shah Sayyed Ibrahim, Nasir Fazli, Malik Nadia Shamshad, Alamzeb Muhammad, Abbas Muhammad, Rehman Inayat Ur, Khuda Fazli, Shah Yasir, Goh Khang Weh, Zeb Alam, Ming Long Chiau

机构信息

Department of Pharmacy, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, Pakistan.

Department of Pharmacy, University of Peshawar, Khyber Pakhtunkhwa 25100, Pakistan.

出版信息

Pharmaceuticals (Basel). 2022 Aug 15;15(8):1005. doi: 10.3390/ph15081005.

DOI:10.3390/ph15081005
PMID:36015153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9415556/
Abstract

Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against (HTD). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity () was performed, which was then followed by the activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound (and thus was selected for studies) with an LD value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD value of 53.57 µM. activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm).

摘要

利什曼病被世界卫生组织(WHO)确认为一类疾病(最具新发性且难以控制),影响98个国家,全球年发病率约为120万例。由于耐药性和细胞毒性,化疗治疗的选择有限。因此,迫切需要寻找新的化合物。在本研究中,我们使用了两种化合物,即10-羟基软骨叶酸和他非诺喹,研究它们对(HTD)的抗利什曼活性。首先,对受试化合物进行了针对THP-1细胞的细胞毒性试验,发现这些化合物是安全的。进行了THP-1细胞内无鞭毛体活性()试验,随后在小鼠皮肤利什曼病(CL)模型中检测了10-羟基软骨叶酸的活性。总共使用了三种浓度,即25、50和100μM,以检测受试化合物对无鞭毛体的活性。10-羟基软骨叶酸被发现是最有效的化合物(因此被选用于研究),孵育48小时后的半数致死剂量(LD)值为43.80μM,而他非诺喹的LD值为53.57μM。通过在感染的BALB/c小鼠的左后足注射10-羟基软骨叶酸进行活性试验,与阴性对照(1.2±0.3mm)相比,其病变大小在统计学上显著降低了58.3%(F = 14.18;= 0.),降至0.70±0.03mm。 02

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