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新型噻唑腙衍生物作为治疗人兽共患犬弓首蛔虫替代方案的发现:体外和计算机模拟评估

Discovery of Novel Thiazolohydrazone Derivatives as an Alternative Option in the Treatment of Zoonotic Toxocara canis: In Vitro and In Silico Evaluation.

作者信息

Eser Mustafa, Osmaniye Derya

机构信息

Health Programs, Faculty of Open Education, Anadolu University, Eskisehir, Turkey.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

出版信息

Vet Med Sci. 2025 Jan;11(1):e70144. doi: 10.1002/vms3.70144.

Abstract

Thiazoles serve as pharmacophores in many molecules that exhibit significant biological activity. This study used in vitro assays and in silico methodologies to identify novel medication candidates for preclinical evaluation of visceral toxocariasis treatment. The objective was to assess the impact of 11 thiazolohydrazone derivative compounds on the larval eggs of Toxocara canis. In addition, the inhibitory effects of these compounds on IL-6 levels in THP-1 cells stimulated with larval eggs have been examined. Compounds indicating the most significant inhibitory effect on IL-6 and a suppressive effect on larval eggs have been included in molecular dynamics studies. The study revealed that, when evaluating all thiazolohydrazone derivatives together, Compounds 3g and 3h possessed the highest antiparasitic efficiency, encouraging further molecular dynamics investigations on these compounds. Consequently, it can be theorised that if the results from this study are corroborated by in vivo studies, new anti-nematodal medication candidates may be identified.

摘要

噻唑在许多具有显著生物活性的分子中充当药效基团。本研究采用体外试验和计算机模拟方法,以鉴定用于内脏弓蛔虫病治疗临床前评估的新型候选药物。目的是评估11种噻唑腙衍生物化合物对犬弓蛔虫幼虫卵的影响。此外,还检测了这些化合物对用幼虫卵刺激的THP-1细胞中IL-6水平的抑制作用。对IL-6具有最显著抑制作用且对幼虫卵有抑制作用的化合物已纳入分子动力学研究。研究表明,当一起评估所有噻唑腙衍生物时,化合物3g和3h具有最高的抗寄生虫效率,这鼓励对这些化合物进行进一步的分子动力学研究。因此,可以推测,如果本研究的结果得到体内研究的证实,可能会鉴定出新的抗线虫候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a36/11706067/1f1323aa6b74/VMS3-11-e70144-g007.jpg

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