The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis
The ever-increasing drug-resistant tuberculosis (TB) has invigorated the focus on the discovery and development of novel therapeutic agents and treatment options. Thiazolidinone-based compounds have shown good antitubercular properties in vitro. Here, we report the design and synthesis of a number o...
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| Format: | Article |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2442703 |
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| author | Nazar Trotsko Agnieszka Głogowska Barbara Kaproń Katarzyna Kozieł Ewa Augustynowicz-Kopeć Agata Paneth |
| author_facet | Nazar Trotsko Agnieszka Głogowska Barbara Kaproń Katarzyna Kozieł Ewa Augustynowicz-Kopeć Agata Paneth |
| author_sort | Nazar Trotsko |
| collection | DOAJ |
| description | The ever-increasing drug-resistant tuberculosis (TB) has invigorated the focus on the discovery and development of novel therapeutic agents and treatment options. Thiazolidinone-based compounds have shown good antitubercular properties in vitro. Here, we report the design and synthesis of a number of new derivatives inspired by the structure of thiazolidine-2,4-dione (TZD). The TZD-based hybrids with the thiosemicarbazone or the pyridinecarbohydrazone moiety were synthesised and their antimycobacterial activity was investigated against the reference H37Rv and two wild Mycobacterium tuberculosis (Mtb) strains. In further studies, a two-drug interaction analysis was also performed for assessing their synergism with the current first-line drugs used for the treatment of TB. It was found that some of the compounds showed high antimycobacterial activity with MICs (0.078–0.283 µM) and a synergistic effect with isoniazid or rifampicin, thereby demonstrating their potential as a promising scaffold for the development of novel coadjuvants for the effective treatment of TB. |
| format | Article |
| id | doaj-art-fb16ada823754feca32a6d883e7a7801 |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-fb16ada823754feca32a6d883e7a78012025-01-03T09:22:22ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2024.2442703The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysisNazar Trotsko0Agnieszka Głogowska1Barbara Kaproń2Katarzyna Kozieł3Ewa Augustynowicz-Kopeć4Agata Paneth5Department of Organic Chemistry, Medical University of Lublin, Lublin, PolandDepartment of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, PolandDepartment of Clinical Genetics, Medical University of Lublin, Lublin, PolandDepartment of Organic Chemistry, Students Research Group, Medical University of Lublin, Lublin, PolandDepartment of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, PolandDepartment of Organic Chemistry, Medical University of Lublin, Lublin, PolandThe ever-increasing drug-resistant tuberculosis (TB) has invigorated the focus on the discovery and development of novel therapeutic agents and treatment options. Thiazolidinone-based compounds have shown good antitubercular properties in vitro. Here, we report the design and synthesis of a number of new derivatives inspired by the structure of thiazolidine-2,4-dione (TZD). The TZD-based hybrids with the thiosemicarbazone or the pyridinecarbohydrazone moiety were synthesised and their antimycobacterial activity was investigated against the reference H37Rv and two wild Mycobacterium tuberculosis (Mtb) strains. In further studies, a two-drug interaction analysis was also performed for assessing their synergism with the current first-line drugs used for the treatment of TB. It was found that some of the compounds showed high antimycobacterial activity with MICs (0.078–0.283 µM) and a synergistic effect with isoniazid or rifampicin, thereby demonstrating their potential as a promising scaffold for the development of novel coadjuvants for the effective treatment of TB.https://www.tandfonline.com/doi/10.1080/14756366.2024.2442703Thiazolidine-2,4-dionesantimycobacterial activitystructure–activity relationshipsynergismcytotoxicity |
| spellingShingle | Nazar Trotsko Agnieszka Głogowska Barbara Kaproń Katarzyna Kozieł Ewa Augustynowicz-Kopeć Agata Paneth The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis Journal of Enzyme Inhibition and Medicinal Chemistry Thiazolidine-2,4-diones antimycobacterial activity structure–activity relationship synergism cytotoxicity |
| title | The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis |
| title_full | The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis |
| title_fullStr | The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis |
| title_full_unstemmed | The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis |
| title_short | The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis |
| title_sort | new thiazolidine 2 4 dione based hybrids with promising antimycobacterial activity design synthesis biological evaluation and drug interaction analysis |
| topic | Thiazolidine-2,4-diones antimycobacterial activity structure–activity relationship synergism cytotoxicity |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2442703 |
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