Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety
Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2...
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2022-09-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/19/6368 |
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| author | Amr S. Abouzied Jehan Y. Al-Humaidi Abdulrahman S Bazaid Husam Qanash Naif K. Binsaleh Abdulwahab Alamri Sheikh Muhammad Ibrahim Sobhi M. Gomha |
| author_facet | Amr S. Abouzied Jehan Y. Al-Humaidi Abdulrahman S Bazaid Husam Qanash Naif K. Binsaleh Abdulwahab Alamri Sheikh Muhammad Ibrahim Sobhi M. Gomha |
| author_sort | Amr S. Abouzied |
| collection | DOAJ |
| description | Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2<i>H</i>)-yl)-3-phenylthiourea (<b>2</b>) was prepared and reacted with various hydrazonoyl halides <b>3a</b>–<b>h,</b> α-haloketones <b>5a</b>–<b>d</b>, 3-chloropentane-2,4-dione <b>7a</b> and ethyl 2-chloro-3-oxobutanoate <b>7b</b>, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles <b>4a</b>–<b>h,</b> 3-phenyl-4-arylthiazoles <b>6a</b>–<b>d</b> and the 4-methyl-3- phenyl-5-substituted thiazoles <b>8a,b</b>, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole <b>4h</b> was found to be most promising and an excellent performer against both cancer cell lines (IC<sub>50</sub> = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC<sub>50</sub> = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK. |
| first_indexed | 2024-03-09T21:25:16Z |
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| id | doaj.art-0ad22941690b432b979024cc6f96a58b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:25:16Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-0ad22941690b432b979024cc6f96a58b2023-11-23T21:10:17ZengMDPI AGMolecules1420-30492022-09-012719636810.3390/molecules27196368Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine MoietyAmr S. Abouzied0Jehan Y. Al-Humaidi1Abdulrahman S Bazaid2Husam Qanash3Naif K. Binsaleh4Abdulwahab Alamri5Sheikh Muhammad Ibrahim6Sobhi M. Gomha7Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81442, Saudi ArabiaDepartment of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi ArabiaDepartment of Medical Laboratory Science, College of Applied Medical Sciences, University of Hail, Hail 55476, Saudi ArabiaDepartment of Medical Laboratory Science, College of Applied Medical Sciences, University of Hail, Hail 55476, Saudi ArabiaDepartment of Medical Laboratory Science, College of Applied Medical Sciences, University of Hail, Hail 55476, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55211, Saudi ArabiaChemistry Department, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaChemistry Department, Faculty of Science, Cairo University, Giza 12613, EgyptPyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2<i>H</i>)-yl)-3-phenylthiourea (<b>2</b>) was prepared and reacted with various hydrazonoyl halides <b>3a</b>–<b>h,</b> α-haloketones <b>5a</b>–<b>d</b>, 3-chloropentane-2,4-dione <b>7a</b> and ethyl 2-chloro-3-oxobutanoate <b>7b</b>, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles <b>4a</b>–<b>h,</b> 3-phenyl-4-arylthiazoles <b>6a</b>–<b>d</b> and the 4-methyl-3- phenyl-5-substituted thiazoles <b>8a,b</b>, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole <b>4h</b> was found to be most promising and an excellent performer against both cancer cell lines (IC<sub>50</sub> = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC<sub>50</sub> = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.https://www.mdpi.com/1420-3049/27/19/6368pyridines1,3,4-thiadiazoles1,3-thiazoleshydrazonoyl halidesmolecular dockinganticancer activity |
| spellingShingle | Amr S. Abouzied Jehan Y. Al-Humaidi Abdulrahman S Bazaid Husam Qanash Naif K. Binsaleh Abdulwahab Alamri Sheikh Muhammad Ibrahim Sobhi M. Gomha Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety Molecules pyridines 1,3,4-thiadiazoles 1,3-thiazoles hydrazonoyl halides molecular docking anticancer activity |
| title | Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety |
| title_full | Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety |
| title_fullStr | Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety |
| title_full_unstemmed | Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety |
| title_short | Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety |
| title_sort | synthesis molecular docking study and cytotoxicity evaluation of some novel 1 3 4 thiadiazole as well as 1 3 thiazole derivatives bearing a pyridine moiety |
| topic | pyridines 1,3,4-thiadiazoles 1,3-thiazoles hydrazonoyl halides molecular docking anticancer activity |
| url | https://www.mdpi.com/1420-3049/27/19/6368 |
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