Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules
In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative <b>3</b>. The as-prepared carbodithioate derivative <b>3</b> is considered to be a key molecule for the preparation of new antipyrine-1,3,4...
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MDPI AG
2023-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/22/7491 |
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| author | Huda R. M. Rashdan Gharieb S. El-Sayyad Ihsan A. Shehadi Aboubakr H. Abdelmonsef |
| author_facet | Huda R. M. Rashdan Gharieb S. El-Sayyad Ihsan A. Shehadi Aboubakr H. Abdelmonsef |
| author_sort | Huda R. M. Rashdan |
| collection | DOAJ |
| description | In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative <b>3</b>. The as-prepared carbodithioate derivative <b>3</b> is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (<b>4</b>–<b>9</b>) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine–pyrimidine hybrid molecule (<b>10</b>). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (<b>11</b>) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (<b>12</b>). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against <i>E. coli</i> β-carbonic anhydrase. The amount of cellular protein released by <i>E. coli</i> is directly correlated to the concentration of compound <b>9</b>, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound <b>9</b>. This finding supports compound <b>9</b>’s antibacterial properties and explains how the formation of holes in the <i>E. coli</i> cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against <i>E. coli</i> β-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (<b>9</b>) declared a greater activity than the other synthesized compounds. |
| first_indexed | 2024-03-09T16:34:14Z |
| format | Article |
| id | doaj.art-5beb7118a927486b856d2cbb940a75ad |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:34:14Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-5beb7118a927486b856d2cbb940a75ad2023-11-24T14:57:55ZengMDPI AGMolecules1420-30492023-11-012822749110.3390/molecules28227491Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based MoleculesHuda R. M. Rashdan0Gharieb S. El-Sayyad1Ihsan A. Shehadi2Aboubakr H. Abdelmonsef3Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Buhouth St., Dokki, Giza 12622, EgyptDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University (ACU), Giza 12566, EgyptChemistry Department, College of Sciences, University of Sharjah, Sharjah 27272, United Arab EmiratesChemistry Department, Faculty of Science, South Valley University, Qena 83523, EgyptIn this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative <b>3</b>. The as-prepared carbodithioate derivative <b>3</b> is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (<b>4</b>–<b>9</b>) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine–pyrimidine hybrid molecule (<b>10</b>). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (<b>11</b>) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (<b>12</b>). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against <i>E. coli</i> β-carbonic anhydrase. The amount of cellular protein released by <i>E. coli</i> is directly correlated to the concentration of compound <b>9</b>, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound <b>9</b>. This finding supports compound <b>9</b>’s antibacterial properties and explains how the formation of holes in the <i>E. coli</i> cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against <i>E. coli</i> β-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (<b>9</b>) declared a greater activity than the other synthesized compounds.https://www.mdpi.com/1420-3049/28/22/7491phenazonemethyl hydrazinecarbodithioateantimicrobial potencymolecular docking |
| spellingShingle | Huda R. M. Rashdan Gharieb S. El-Sayyad Ihsan A. Shehadi Aboubakr H. Abdelmonsef Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules Molecules phenazone methyl hydrazinecarbodithioate antimicrobial potency molecular docking |
| title | Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules |
| title_full | Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules |
| title_fullStr | Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules |
| title_full_unstemmed | Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules |
| title_short | Antimicrobial Potency and <i>E. coli</i> β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules |
| title_sort | antimicrobial potency and i e coli i β carbonic anhydrase inhibition efficacy of phenazone based molecules |
| topic | phenazone methyl hydrazinecarbodithioate antimicrobial potency molecular docking |
| url | https://www.mdpi.com/1420-3049/28/22/7491 |
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