Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents
In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (<b>4</b>–<b>9</b>), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL)...
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| author | Dagmara Ziembicka Katarzyna Gobis Małgorzata Szczesio Andrzej Olczak Ewa Augustynowicz-Kopeć Agnieszka Głogowska Izabela Korona-Głowniak Krzysztof Bojanowski |
| author_facet | Dagmara Ziembicka Katarzyna Gobis Małgorzata Szczesio Andrzej Olczak Ewa Augustynowicz-Kopeć Agnieszka Głogowska Izabela Korona-Głowniak Krzysztof Bojanowski |
| author_sort | Dagmara Ziembicka |
| collection | DOAJ |
| description | In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (<b>4</b>–<b>9</b>), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds <b>5</b> and <b>7</b>, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds <b>5</b> and <b>7</b> were identified as leading structures for further research on antituberculosis drugs with extended effects. |
| first_indexed | 2024-03-11T09:54:37Z |
| format | Article |
| id | doaj.art-0c32aa9acdbc4155859f75e769ee6175 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-11T09:54:37Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-0c32aa9acdbc4155859f75e769ee61752023-11-16T15:51:47ZengMDPI AGMaterials1996-19442023-01-0116144810.3390/ma16010448Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis AgentsDagmara Ziembicka0Katarzyna Gobis1Małgorzata Szczesio2Andrzej Olczak3Ewa Augustynowicz-Kopeć4Agnieszka Głogowska5Izabela Korona-Głowniak6Krzysztof Bojanowski7Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 107 Gen. Hallera Ave, 80-416 Gdansk, PolandDepartment of Organic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 107 Gen. Hallera Ave, 80-416 Gdansk, PolandInstitute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Żeromskiego St, 90-924 Lodz, PolandInstitute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Żeromskiego St, 90-924 Lodz, PolandDepartment of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka St, 01-138 Warsaw, PolandDepartment of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 Płocka St, 01-138 Warsaw, PolandDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Lublin, 1 Chodźki St, 20-093 Lublin, PolandSunny BioDiscovery Inc., 972 East Main St, Santa Paula, CA 93060, USAIn this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (<b>4</b>–<b>9</b>), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds <b>5</b> and <b>7</b>, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds <b>5</b> and <b>7</b> were identified as leading structures for further research on antituberculosis drugs with extended effects.https://www.mdpi.com/1996-1944/16/1/448synthesispyridinethiosemicarbazonetuberculostatic activityantimicrobial activitycytotoxic activity |
| spellingShingle | Dagmara Ziembicka Katarzyna Gobis Małgorzata Szczesio Andrzej Olczak Ewa Augustynowicz-Kopeć Agnieszka Głogowska Izabela Korona-Głowniak Krzysztof Bojanowski Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents Materials synthesis pyridine thiosemicarbazone tuberculostatic activity antimicrobial activity cytotoxic activity |
| title | Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents |
| title_full | Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents |
| title_fullStr | Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents |
| title_full_unstemmed | Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents |
| title_short | Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents |
| title_sort | synthesis and structure activity relationship of 2 6 disubstituted thiosemicarbazone derivatives of pyridine as potential antituberculosis agents |
| topic | synthesis pyridine thiosemicarbazone tuberculostatic activity antimicrobial activity cytotoxic activity |
| url | https://www.mdpi.com/1996-1944/16/1/448 |
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