作为潜在抗阿卡他米巴药剂的唑基化合物

IF 3.597 Q2 Pharmacology, Toxicology and Pharmaceutics
MedChemComm Pub Date : 2024-04-03 DOI:10.1039/D4MD00029C
Balsam Qubais Saeed, Rania Hamdy, Noor Akbar, Sreedevi Edathadan Sajeevan, Naveed Ahmed Khan and Sameh S. M. Soliman
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引用次数: 0

摘要

卡斯特阿米巴原虫是一种具有公共卫生影响的机会性病原体,主要是因为它具有侵袭性和非特异性症状。我们的研究重点是唑类化合物,尤其是具有三唑支架的化合物作为抗阿米巴药剂的潜力。在 10 个化合物中,化合物 T1 和 T8 具有有效的抗阿卡米巴活性,其 MIC50 值分别为 125.37 和 143.92 μg mL-1。有趣的是,化合物 T1、T4、T5 和 T8 显示出很强的抗卵巢囊肿活性,MIC50 分别为 32.01、85.53、19.54 和 80.57 μg mL-1,同时对人体细胞的细胞毒性有限。该研究强调了噻唑类化合物 T1、T4、T5 和 T8 作为抗阿卡他米巴药剂的潜力,它们既能消除阿米巴的活力,又能防止阿米巴外寄生,通过保留阿米巴的潜伏囊形态,使它们暴露在被免疫系统消灭的危险中。值得注意的是,化合物 T1、T4、T5 和 T8 显示出最佳的分子特性、适度的口服生物利用度以及与阿米巴 CYP51 形成稳定的复合物。它们还显示出卓越的结合相互作用。要了解它们的作用机制并优化其抗棘阿米巴感染的功效,还需要进一步的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Azole-based compounds as potential anti-Acanthamoeba agents†

Azole-based compounds as potential anti-Acanthamoeba agents†

Acanthamoeba castellanii is an opportunistic pathogen with public health implications, largely due to its invasive nature and non-specific symptoms. Our study focuses on the potential of azole compounds, particularly those with triazole scaffolds, as anti-amoebic agents. Out of 10 compounds, compounds T1 and T8 exhibited effective anti-Acanthamoeba activity with MIC50 values of 125.37 and 143.92 μg mL−1, respectively. Interestingly, compounds T1, T4, T5 and T8 revealed profound anti-excystation activity with MIC50 at 32.01, 85.53, 19.54 and 80.57 μg mL−1, respectively, alongside limited cytotoxicity to human cells. The study underscores the potential of T1, T4, T5, and T8, thiazole-based compounds, as anti-Acanthamoeba agents by both eliminating amoeba viability and preventing excystation, via preserving the amoeba in its latent cyst form, exposing them to elimination by the immune system. Notably, compounds T1, T4, T5, and T8 showed optimal molecular properties, moderate oral bioavailability, and stable complex formation with Acanthamoeba CYP51. They also display superior binding interactions. Further research is needed to understand their mechanisms and optimize their efficacy against Acanthamoeba infections.

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来源期刊
MedChemComm
MedChemComm BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
4.70
自引率
0.00%
发文量
0
审稿时长
2.2 months
期刊介绍: Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry. In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.
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