Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives
Fifteen 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives <b>3a</b>–<b>d</b> and sulfonyl hydrazones <b>5a</b>–<b>k</b> were synthesized. They were characterized by <sup>1</sup>H-NMR, <sup>13</sup>C NMR, and HRMS. <i>...
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MDPI AG
2022-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/5/562 |
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| author | Violina T. Angelova Tania Pencheva Nikolay Vassilev Elena K-Yovkova Rositsa Mihaylova Boris Petrov Violeta Valcheva |
| author_facet | Violina T. Angelova Tania Pencheva Nikolay Vassilev Elena K-Yovkova Rositsa Mihaylova Boris Petrov Violeta Valcheva |
| author_sort | Violina T. Angelova |
| collection | DOAJ |
| description | Fifteen 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives <b>3a</b>–<b>d</b> and sulfonyl hydrazones <b>5a</b>–<b>k</b> were synthesized. They were characterized by <sup>1</sup>H-NMR, <sup>13</sup>C NMR, and HRMS. <i>Mycobacterium tuberculosis</i> strain H37Rv was used to assess their antimycobacterial activity. All compounds demonstrated significant minimum inhibitory concentrations (MIC) from 0.07 to 0.32 µM, comparable to those of isoniazid. The cytotoxicity was evaluated using the standard MTT-dye reduction test against human embryonic kidney cells HEK-293T and mouse fibroblast cell line CCL-1. 4-Hydroxy-3-methoxyphenyl substituted 1,2,3-thiadiazole-based hydrazone derivative <b>3d</b> demonstrated the highest antimycobacterial activity (MIC = 0.0730 µM) and minimal associated cytotoxicity against two normal cell lines (selectivity index SI = 3516, HEK-293, and SI = 2979, CCL-1). The next in order were sulfonyl hydrazones <b>5g</b> and <b>5k</b> with MIC 0.0763 and 0.0716 µM, respectively, which demonstrated comparable minimal cytotoxicity. All compounds were subjected to ADME/Tox computational predictions, which showed that all compounds corresponded to Lipinski’s Ro5, and none were at risk of toxicity. The suitable scores of molecular docking performed on two crystallographic structures of enoyl-ACP reductase (InhA) provide promising insight into possible interaction with the InhA receptor. The 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives and sulfonyl hydrazones proved to be new classes of lead compounds having the potential of novel candidate antituberculosis drugs. |
| first_indexed | 2024-03-10T03:28:38Z |
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| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T03:28:38Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
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| series | Antibiotics |
| spelling | doaj.art-bec4c4c69ea34f0db031b0bbee7cda2c2023-11-23T09:47:49ZengMDPI AGAntibiotics2079-63822022-04-0111556210.3390/antibiotics11050562Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone DerivativesViolina T. Angelova0Tania Pencheva1Nikolay Vassilev2Elena K-Yovkova3Rositsa Mihaylova4Boris Petrov5Violeta Valcheva6Department of Chemistry, Faculty of Pharmacy, Medical University, 1431 Sofia, BulgariaDepartment of QSAR and Molecular Modeling, Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaLaboratory “Nuclear Magnetic Resonance”, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaFaculty of Computer Systems and Technologies, Technical University, 1756 Sofia, BulgariaLaboratory “Drug Metabolism and Drug Toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University, 1431 Sofia, BulgariaDepartment of Chemistry, Faculty of Pharmacy, Medical University, 1431 Sofia, BulgariaLaboratory of Molecular Biology of Mycobacteria, Department of Infectious Microbiology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaFifteen 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives <b>3a</b>–<b>d</b> and sulfonyl hydrazones <b>5a</b>–<b>k</b> were synthesized. They were characterized by <sup>1</sup>H-NMR, <sup>13</sup>C NMR, and HRMS. <i>Mycobacterium tuberculosis</i> strain H37Rv was used to assess their antimycobacterial activity. All compounds demonstrated significant minimum inhibitory concentrations (MIC) from 0.07 to 0.32 µM, comparable to those of isoniazid. The cytotoxicity was evaluated using the standard MTT-dye reduction test against human embryonic kidney cells HEK-293T and mouse fibroblast cell line CCL-1. 4-Hydroxy-3-methoxyphenyl substituted 1,2,3-thiadiazole-based hydrazone derivative <b>3d</b> demonstrated the highest antimycobacterial activity (MIC = 0.0730 µM) and minimal associated cytotoxicity against two normal cell lines (selectivity index SI = 3516, HEK-293, and SI = 2979, CCL-1). The next in order were sulfonyl hydrazones <b>5g</b> and <b>5k</b> with MIC 0.0763 and 0.0716 µM, respectively, which demonstrated comparable minimal cytotoxicity. All compounds were subjected to ADME/Tox computational predictions, which showed that all compounds corresponded to Lipinski’s Ro5, and none were at risk of toxicity. The suitable scores of molecular docking performed on two crystallographic structures of enoyl-ACP reductase (InhA) provide promising insight into possible interaction with the InhA receptor. The 4-methyl-1,2,3-thiadiazole-based hydrazone derivatives and sulfonyl hydrazones proved to be new classes of lead compounds having the potential of novel candidate antituberculosis drugs.https://www.mdpi.com/2079-6382/11/5/562antimycobacterial activityADME/Tox predictionscytotoxicityhydrazide-hydrazone derivativessulfonyl hydrazone derivativesmolecular docking |
| spellingShingle | Violina T. Angelova Tania Pencheva Nikolay Vassilev Elena K-Yovkova Rositsa Mihaylova Boris Petrov Violeta Valcheva Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives Antibiotics antimycobacterial activity ADME/Tox predictions cytotoxicity hydrazide-hydrazone derivatives sulfonyl hydrazone derivatives molecular docking |
| title | Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives |
| title_full | Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives |
| title_fullStr | Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives |
| title_full_unstemmed | Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives |
| title_short | Development of New Antimycobacterial Sulfonyl Hydrazones and 4-Methyl-1,2,3-thiadiazole-Based Hydrazone Derivatives |
| title_sort | development of new antimycobacterial sulfonyl hydrazones and 4 methyl 1 2 3 thiadiazole based hydrazone derivatives |
| topic | antimycobacterial activity ADME/Tox predictions cytotoxicity hydrazide-hydrazone derivatives sulfonyl hydrazone derivatives molecular docking |
| url | https://www.mdpi.com/2079-6382/11/5/562 |
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