β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis.

IF 2 Q2 AGRICULTURE, DAIRY & ANIMAL SCIENCE
Veterinary World Pub Date : 2025-03-01 Epub Date: 2025-03-31 DOI:10.14202/vetworld.2025.731-745
Lyudmila Kayukova, Venera Bismilda, Kairat Turgenbayev, Assem Uzakova, Gulnur Baitursynova, Umirzak Jussipbekov, Meruyert Mukanova, Lyailya Chingissova, Gulnur Dyussembayeva, Assiya Borsynbayeva, Azamat Yerlanuly, Ablay Auyezov
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引用次数: 0

Abstract

Background and aim: Tuberculosis (TB) remains a significant global health challenge, with increasing incidences of drug-sensitive (DS) and multidrug-resistant (MDR) TB. In addition, Mycobacterium bovis-induced zoonotic TB (zTB) presents treatment difficulties due to its resistance to pyrazinamide and the prolonged treatment duration required. This study aims to evaluate the antitubercular potential of β-aminopropioamidoxime derivatives against DS and MDR M. tuberculosis and M. bovis strains, and utilizing the SwissADME prognostic tool to predict the drug- and lead-likeness of the described compounds.

Materials and methods: Six β-aminopropioamidoxime derivatives were synthesized through O-aroylation of amidoxime followed by dehydration to form 1,2,4-oxadiazoles. The compounds were tested in vitro against DS, MDR M. tuberculosis, and M. bovis using Sotton's liquid medium and subcultured on dense Lowenstein-Jensen medium. SwissADME was used to predict drug-likeness and pharmacokinetic properties.

Results: The derivatives exhibited significant antitubercular activity, with in vitro efficacy 5-100 times greater than rifampicin. 1,2,4-oxadiazoles with para-bromo and meta-chloro substituents demonstrated the highest activity against DS and MDR M. tuberculosis, while O-para-toluoyl-β-(morpholin-1-yl)propioamidoxime salts (hydrochloride, oxalate and citrate) were 10 times more active against M. bovis. SwissADME analysis confirmed favorable pharmacokinetic properties, including high gastrointestinal absorption and drug-likeness, with lead-likeness identified in four compounds.

Conclusion: The study presents β-aminopropioamidoxime derivatives as promising candidates for antitubercular therapy against both human and zTB. Their enhanced activity, oral bioavailability, and potential integration into new treatment regimens underscore their therapeutic relevance. Further in vivo studies are recommended to validate their efficacy and safety for clinical applications.

β-氨基丙酰胺肟衍生物作为潜在的抗结核药物对结核分枝杆菌和牛分枝杆菌引起的人畜共患感染。
背景与目的:随着药敏(DS)和耐多药(MDR)结核病的发病率不断上升,结核病(TB)仍然是一个重大的全球卫生挑战。此外,牛分枝杆菌诱导的人畜共患结核(zTB)由于其对吡嗪酰胺的耐药性和所需的治疗时间延长而带来治疗困难。本研究旨在评价β-氨基丙胺肟衍生物对DS和MDR结核分枝杆菌和牛分枝杆菌菌株的抗结核潜力,并利用SwissADME预测工具预测所述化合物的药物和铅的相似性。材料与方法:以偕胺肟为原料,经o -芳基化脱水合成6个β-氨基丙胺肟衍生物,得到1,2,4-恶二唑。用Sotton液体培养基和密集的Lowenstein-Jensen培养基进行继代培养,测试化合物对DS、耐多药结核分枝杆菌和牛分枝杆菌的体外抗性。使用SwissADME预测药物相似性和药代动力学性质。结果:该衍生物具有明显的抗结核活性,其体外药效是利福平的5-100倍。具有对溴和间氯取代基的1,2,4-恶二唑对DS和MDR结核分枝杆菌的活性最高,而o -对甲苯基-β-(morpholin-1-yl)丙胺肟盐(盐酸盐、草酸盐和柠檬酸盐)对牛分枝杆菌的活性高10倍。SwissADME分析证实了良好的药代动力学特性,包括高胃肠道吸收和药物相似,其中四种化合物与铅相似。结论:β-氨基丙胺肟衍生物作为抗结核药物治疗人类和zTB的潜在候选药物。其增强的活性,口服生物利用度和潜在的整合到新的治疗方案强调其治疗相关性。建议进一步的体内研究以验证其临床应用的有效性和安全性。
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来源期刊
Veterinary World
Veterinary World Multiple-
CiteScore
3.60
自引率
12.50%
发文量
317
审稿时长
16 weeks
期刊介绍: Veterinary World publishes high quality papers focusing on Veterinary and Animal Science. The fields of study are bacteriology, parasitology, pathology, virology, immunology, mycology, public health, biotechnology, meat science, fish diseases, nutrition, gynecology, genetics, wildlife, laboratory animals, animal models of human infections, prion diseases and epidemiology. Studies on zoonotic and emerging infections are highly appreciated. Review articles are highly appreciated. All articles published by Veterinary World are made freely and permanently accessible online. All articles to Veterinary World are posted online immediately as they are ready for publication.
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