Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles
A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-07-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/22/7/1211 |
| _version_ | 1819170471544881152 |
|---|---|
| author | Zeinab A. Muhammad Mastoura M. Edrees Rasha A. M. Faty Sobhi M. Gomha Seham S. Alterary Yahia N. Mabkhot |
| author_facet | Zeinab A. Muhammad Mastoura M. Edrees Rasha A. M. Faty Sobhi M. Gomha Seham S. Alterary Yahia N. Mabkhot |
| author_sort | Zeinab A. Muhammad |
| collection | DOAJ |
| description | A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results. |
| first_indexed | 2024-12-22T19:35:55Z |
| format | Article |
| id | doaj.art-338a433166c44227a95b33885ddb34d9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T19:35:55Z |
| publishDate | 2017-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-338a433166c44227a95b33885ddb34d92022-12-21T18:14:58ZengMDPI AGMolecules1420-30492017-07-01227121110.3390/molecules22071211molecules22071211Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based HeterocyclesZeinab A. Muhammad0Mastoura M. Edrees1Rasha A. M. Faty2Sobhi M. Gomha3Seham S. Alterary4Yahia N. Mabkhot5Department of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12311, EgyptDepartment of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza 12311, EgyptDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaA series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 8, 4e and 7b have promising activities against the A-549 cell line (IC50 values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound 7b has promising activity against the HepG-2 cell lines (IC50 = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results.https://www.mdpi.com/1420-3049/22/7/1211morpholinechalconesthioneshydrazonoyl halidesanticancer activitymolecular docking |
| spellingShingle | Zeinab A. Muhammad Mastoura M. Edrees Rasha A. M. Faty Sobhi M. Gomha Seham S. Alterary Yahia N. Mabkhot Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles Molecules morpholine chalcones thiones hydrazonoyl halides anticancer activity molecular docking |
| title | Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles |
| title_full | Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles |
| title_fullStr | Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles |
| title_full_unstemmed | Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles |
| title_short | Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles |
| title_sort | synthesis antitumor evaluation and molecular docking of new morpholine based heterocycles |
| topic | morpholine chalcones thiones hydrazonoyl halides anticancer activity molecular docking |
| url | https://www.mdpi.com/1420-3049/22/7/1211 |
| work_keys_str_mv | AT zeinabamuhammad synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles AT mastouramedrees synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles AT rashaamfaty synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles AT sobhimgomha synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles AT sehamsalterary synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles AT yahianmabkhot synthesisantitumorevaluationandmoleculardockingofnewmorpholinebasedheterocycles |