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

L. A. Kаyukova, Venera Bismilda, Kairat Altynbekovich Turgenbayev, Assem Uzakova, Gulnur Baitursynova, U.Zh. Jussipbekov, M. S. Mukanova, Lyailya Chingissova, Dyussembayeva Gulnur Toktargazinovna, Assiya Borsynbayeva

2 more authors

Azamat Yerlanuly, A Auezov

Veterinary World, 2025

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.14202/vetworld.2025.731-745
Data confidence 85 high
How this score is calculated

It is built from checkable properties of the record itself: whether the article has a DOI, how many independent sources confirmed its data, whether the required fields are filled in, and how recent the latest confirmation is. Disagreement between sources and a missing identifier lower it. A value of 80 or above means the record was published without further checking; 60 to 79 means it is published at reduced confidence, with a manual check advisable. A record verified by an editor by hand is never pushed below 90 by a recalculation. This scores our data about the article, not the article itself.

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 Mycobacterium 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. Keywords: antitubercular agents, Mycobacterium bovis, Mycobacterium tuberculosis, SwissADME, tuberculosis, β-aminopropioamidoximes.