Novel Antimicrobial and Antitumor Agents Bearing Pyridine-1,2,4-triazole-3-thione-hydrazone Scaffold: Synthesis, Biological Evaluation, and Molecular Docking Investigation
A series of target 4-substituted-5-(2-(pyridine-2-ylamino)ethyl)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thiones and their chloro analogs <b>7</b>–<b>21</b> were synthesized in a reaction of the selected aldehydes with the corresponding 4-amino-1,2,4-triazole-3-thi...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/14/12/1529 |
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| Summary: | A series of target 4-substituted-5-(2-(pyridine-2-ylamino)ethyl)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thiones and their chloro analogs <b>7</b>–<b>21</b> were synthesized in a reaction of the selected aldehydes with the corresponding 4-amino-1,2,4-triazole-3-thiones <b>5</b> and <b>6</b>, which were obtained from 3-(pyridin-2-ylamino)propanoic acid (<b>3</b>) or 3-((5-chloropyridin-2-yl)amino)propanoic acid (<b>4</b>), respectively, with thioacetohydrazide. The antibacterial and antifungal activities of the synthesized hydrazones were screened against the bacteria <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Mycobacterium luteum</i> and the fungi <i>Candida tenuis</i> and <i>Aspergillus niger</i> by agar diffusion and serial dilution methods. 4-Amino-5-(2-((5-chloropyridin-2-yl)amino)ethyl)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thione (<b>6</b>) and 4-(benzylideneamino)-5-(2-(pyridin-2-ylamino)ethyl)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thione (<b>7</b>) were identified as exceptionally active (MIC 0.9 µg/mL) against the fungus <i>C. tenuis.</i> 5-Chloropyridine derivatives bearing 4-benzylidene <b>8</b>, 2-nitrobenzylidene <b>10</b>, pyridinylmethylene <b>16</b>, and 4-methylthiobenzylidene <b>21</b> moieties showed very high antibacterial activity (MIC 3.9 µg/mL) against the <i>M. luteum</i> strain. The cell viability screening of the synthesized compounds using triple-negative breast cancer MDA-MB-231 and glioblastoma U-87 cell lines by MTT assay identified three active hydrazones, of which 5-(2-(pyridin-2-ylamino)ethyl)-4-((pyridin-3-ylmethylene)amino)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thione (<b>15</b>) had the highest effect on the viability of cells (IC<sub>50</sub> value 39.2 ± 1.7 μM against MDA-MD-231). The in silico molecular modeling results suggested that these three most active hydrazones might have influenced the mitogen-activated protein kinase pathway through the inhibition of BRAF and MEK serine–threonine protein kinases. 5-(2-((5-Chloropyridin-2-yl)amino)ethyl)-4-((4-(methylthio)benzylidene)amino)-2,4-dihydro-3<i>H</i>-1,2,4-triazole-3-thione (<b>21</b>) demonstrated the highest affinity among them. |
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| ISSN: | 2218-273X |