Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity
Objectives. To develop the procedures for synthesis of hybrid molecules with potential anti-tubercular activity containing heterocyclic cores of 4-nitroimidazole and 1,3,4-thiadiazole within the framework of a double-drug strategy and predict bioactivity of target structures and drug-likeness physic...
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MIREA - Russian Technological University
2023-08-01
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| Series: | Тонкие химические технологии |
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| Online Access: | https://www.finechem-mirea.ru/jour/article/view/1971 |
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| author | T. S. Vedekhina M. V. Chudinov A. Yu. Lukin |
| author_facet | T. S. Vedekhina M. V. Chudinov A. Yu. Lukin |
| author_sort | T. S. Vedekhina |
| collection | DOAJ |
| description | Objectives. To develop the procedures for synthesis of hybrid molecules with potential anti-tubercular activity containing heterocyclic cores of 4-nitroimidazole and 1,3,4-thiadiazole within the framework of a double-drug strategy and predict bioactivity of target structures and drug-likeness physicochemical parameters.Methods. Target compounds were prepared by classical organic synthesis methods. The structure of the obtained compounds was characterized by melting points, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The calculation of the physicochemical parameters of the target compounds and prediction of their biological activity were carried out using publicly available software for cheminformatics and molecular modeling.Results. Acylation of propargylamine with (2-methyl-4-nitro-1H-imidazol-1-yl)acetic and (4-nitro-1H-imidazol-1-yl)acetic acids provided the corresponding amides, which were cyclized with seven different benzylamines in the presence of zinc triflate. In this way, seven new compounds were obtained at 20–30% yields. Ten arylamines were acylated with chloroacetyl chloride and the resulting chloroacetamides were converted into corresponding thio-oxahydrazides by the Willgerodt–Kindler reaction. Following acylation by (4-nitro-1H-imidazol-1-yl)acetic acid, these compounds were converted into the target hybrid imidazolyl-thiadiazoles at 29–54% yields.Conclusions. Two series of new heterocyclic compounds with a hybrid structure including a privileged 4-nitroimidazole moiety linked to the second heterocycle, imidazole, or thiadiazole, were obtained. The synthesis and characterization of compounds by physicochemical methods was aimed at searching for anti-tuberculosis activity. The bioactivity potential of target compounds was demonstrated by preliminary calculations performed using public prognostic programs. |
| format | Article |
| id | doaj-art-5cd86b005c2c4b1da83acb7181d19269 |
| institution | Kabale University |
| issn | 2410-6593 2686-7575 |
| language | Russian |
| publishDate | 2023-08-01 |
| publisher | MIREA - Russian Technological University |
| record_format | Article |
| series | Тонкие химические технологии |
| spelling | doaj-art-5cd86b005c2c4b1da83acb7181d192692025-08-20T03:56:32ZrusMIREA - Russian Technological UniversityТонкие химические технологии2410-65932686-75752023-08-0118321922910.32362/2410-6593-2023-18-3-219-2291717Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activityT. S. Vedekhina0M. V. Chudinov1A. Yu. Lukin2Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological AgencyMIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)MIREA – Russian Technological University (M.V. Lomonosov Institute of Fine Chemical Technologies)Objectives. To develop the procedures for synthesis of hybrid molecules with potential anti-tubercular activity containing heterocyclic cores of 4-nitroimidazole and 1,3,4-thiadiazole within the framework of a double-drug strategy and predict bioactivity of target structures and drug-likeness physicochemical parameters.Methods. Target compounds were prepared by classical organic synthesis methods. The structure of the obtained compounds was characterized by melting points, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The calculation of the physicochemical parameters of the target compounds and prediction of their biological activity were carried out using publicly available software for cheminformatics and molecular modeling.Results. Acylation of propargylamine with (2-methyl-4-nitro-1H-imidazol-1-yl)acetic and (4-nitro-1H-imidazol-1-yl)acetic acids provided the corresponding amides, which were cyclized with seven different benzylamines in the presence of zinc triflate. In this way, seven new compounds were obtained at 20–30% yields. Ten arylamines were acylated with chloroacetyl chloride and the resulting chloroacetamides were converted into corresponding thio-oxahydrazides by the Willgerodt–Kindler reaction. Following acylation by (4-nitro-1H-imidazol-1-yl)acetic acid, these compounds were converted into the target hybrid imidazolyl-thiadiazoles at 29–54% yields.Conclusions. Two series of new heterocyclic compounds with a hybrid structure including a privileged 4-nitroimidazole moiety linked to the second heterocycle, imidazole, or thiadiazole, were obtained. The synthesis and characterization of compounds by physicochemical methods was aimed at searching for anti-tuberculosis activity. The bioactivity potential of target compounds was demonstrated by preliminary calculations performed using public prognostic programs.https://www.finechem-mirea.ru/jour/article/view/1971nitroimidazolesbiimidazoles1,3,4-thiadiazolesn-propargylamidesthiosemicarbazideszinc triflate |
| spellingShingle | T. S. Vedekhina M. V. Chudinov A. Yu. Lukin Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity Тонкие химические технологии nitroimidazoles biimidazoles 1,3,4-thiadiazoles n-propargylamides thiosemicarbazides zinc triflate |
| title | Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity |
| title_full | Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity |
| title_fullStr | Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity |
| title_full_unstemmed | Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity |
| title_short | Design and synthesis of 4-nitroimidazole derivatives with potential antitubercular activity |
| title_sort | design and synthesis of 4 nitroimidazole derivatives with potential antitubercular activity |
| topic | nitroimidazoles biimidazoles 1,3,4-thiadiazoles n-propargylamides thiosemicarbazides zinc triflate |
| url | https://www.finechem-mirea.ru/jour/article/view/1971 |
| work_keys_str_mv | AT tsvedekhina designandsynthesisof4nitroimidazolederivativeswithpotentialantitubercularactivity AT mvchudinov designandsynthesisof4nitroimidazolederivativeswithpotentialantitubercularactivity AT ayulukin designandsynthesisof4nitroimidazolederivativeswithpotentialantitubercularactivity |