β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis
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 an...
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Veterinary World
2025-03-01
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| Series: | Veterinary World |
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| Online Access: | https://www.veterinaryworld.org/Vol.18/March-2025/19.pdf |
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| author | Lyudmila Kayukova Venera Bismilda Kairat Turgenbayev Asem Uzakova Gulnur Baitursynova Umirzak Jussipbekov Meruyert Mukanova Lyailya Chingissova Gulnur Dyussembayeva Assiya Borsynbayeva Azamat Yerlanuly Ablay Auyezov |
| author_facet | Lyudmila Kayukova Venera Bismilda Kairat Turgenbayev Asem Uzakova Gulnur Baitursynova Umirzak Jussipbekov Meruyert Mukanova Lyailya Chingissova Gulnur Dyussembayeva Assiya Borsynbayeva Azamat Yerlanuly Ablay Auyezov |
| author_sort | Lyudmila Kayukova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-edeb6392e464439eb9cb7575b58cf42d |
| institution | DOAJ |
| issn | 0972-8988 2231-0916 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Veterinary World |
| record_format | Article |
| series | Veterinary World |
| spelling | doaj-art-edeb6392e464439eb9cb7575b58cf42d2025-08-20T03:08:31ZengVeterinary WorldVeterinary World0972-89882231-09162025-03-0118373174510.14202/vetworld.2025.731-745β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovisLyudmila Kayukova0https://orcid.org/0000-0002-1900-1228Venera Bismilda1https://orcid.org/0000-0003-3130-9812Kairat Turgenbayev2https://orcid.org/0000-0002-0982-1863Asem Uzakova3https://orcid.org/0000-0002-9664-0912Gulnur Baitursynova4https://orcid.org/0000-0002-8883-0695Umirzak Jussipbekov5https://orcid.org/0000-0002-2354-9878Meruyert Mukanova6https://orcid.org/0000-0003-3128-1311Lyailya Chingissova7https://orcid.org/0000-0002-1164-2661Gulnur Dyussembayeva8https://orcid.org/0000-0003-2721-997XAssiya Borsynbayeva9https://orcid.org/0000-0002-2722-2020Azamat Yerlanuly10https://orcid.org/0009-0009-5482-7621Ablay Auyezov11https://orcid.org/0000-0001-9983-124XJSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.National Scientific Center of Phthisiopulmonology, Ministry of Health of the Republic of Kazakhstan, National Reference Bacteriological Laboratory, Almaty, Kazakhstan.LLP Scientific and Production Center BioVet, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.National Scientific Center of Phthisiopulmonology, Ministry of Health of the Republic of Kazakhstan, National Reference Bacteriological Laboratory, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.LLP Scientific and Production Center BioVet, Almaty, Kazakhstan.JSC A.B. Bekturov Institute of Chemical Sciences, Laboratory of Chemistry of Synthetic and Natural Drug Substances, Almaty, Kazakhstan.National Scientific Center of Phthisiopulmonology, Ministry of Health of the Republic of Kazakhstan, National Reference Bacteriological Laboratory, Almaty, Kazakhstan.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.https://www.veterinaryworld.org/Vol.18/March-2025/19.pdfantitubercular agentsmycobacterium bovismycobacterium tuberculosisswissadmetuberculosisβ-aminopropioamidoximes |
| spellingShingle | Lyudmila Kayukova Venera Bismilda Kairat Turgenbayev Asem Uzakova Gulnur Baitursynova Umirzak Jussipbekov Meruyert Mukanova Lyailya Chingissova Gulnur Dyussembayeva Assiya Borsynbayeva Azamat Yerlanuly Ablay Auyezov β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis Veterinary World antitubercular agents mycobacterium bovis mycobacterium tuberculosis swissadme tuberculosis β-aminopropioamidoximes |
| title | β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis |
| title_full | β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis |
| title_fullStr | β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis |
| title_full_unstemmed | β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis |
| title_short | β-Aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by Mycobacterium tuberculosis and Mycobacterium bovis |
| title_sort | β aminopropioamidoximes derivatives as potential antitubercular agents against anthropozoonotic infections caused by mycobacterium tuberculosis and mycobacterium bovis |
| topic | antitubercular agents mycobacterium bovis mycobacterium tuberculosis swissadme tuberculosis β-aminopropioamidoximes |
| url | https://www.veterinaryworld.org/Vol.18/March-2025/19.pdf |
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