Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents
In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223000734 |
| _version_ | 1811159970368978944 |
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| author | Ashraf A. Aly Mohammed B. Alshammari Akil Ahmad Hesham A. M. Gomaa Bahaa G. M. Youssif Stefan Bräse Mahmoud A. A. Ibrahim Asmaa H. Mohamed |
| author_facet | Ashraf A. Aly Mohammed B. Alshammari Akil Ahmad Hesham A. M. Gomaa Bahaa G. M. Youssif Stefan Bräse Mahmoud A. A. Ibrahim Asmaa H. Mohamed |
| author_sort | Ashraf A. Aly |
| collection | DOAJ |
| description | In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI50 values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI50 = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAFV600E. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAFV600E with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability. |
| first_indexed | 2024-04-10T05:49:45Z |
| format | Article |
| id | doaj.art-6f2d3d5650884a28a154186373f67503 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-10T05:49:45Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-6f2d3d5650884a28a154186373f675032023-03-05T04:24:02ZengElsevierArabian Journal of Chemistry1878-53522023-04-01164104612Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agentsAshraf A. Aly0Mohammed B. Alshammari1Akil Ahmad2Hesham A. M. Gomaa3Bahaa G. M. Youssif4Stefan Bräse5Mahmoud A. A. Ibrahim6Asmaa H. Mohamed7Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt; Corresponding authors at: Chemistry Department, Faculty of Science, Minia University, 61519, El-Minia, Egypt(A.A. Aly), Institute of Organic Chemistry, Karlsruher Institut fur Technologie, 76131 Karlsruhe, Germany(S. Bräse), Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt(B.G.M. Youssif).Chemistry Department, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, Al-Kharij, Saudi ArabiaChemistry Department, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, Al-Kharij, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi ArabiaPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt; Corresponding authors at: Chemistry Department, Faculty of Science, Minia University, 61519, El-Minia, Egypt(A.A. Aly), Institute of Organic Chemistry, Karlsruher Institut fur Technologie, 76131 Karlsruhe, Germany(S. Bräse), Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt(B.G.M. Youssif).Institute of Organic Chemistry, Karlsruher Institut fur Technologie, 76131 Karlsruhe, Germany; Institute of Biological and Chemical Systems (IBCS-FMS), Karlsruhe Institute of Technology, 76344 Eggenstein Leopoldshafen, Germany; Corresponding authors at: Chemistry Department, Faculty of Science, Minia University, 61519, El-Minia, Egypt(A.A. Aly), Institute of Organic Chemistry, Karlsruher Institut fur Technologie, 76131 Karlsruhe, Germany(S. Bräse), Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt(B.G.M. Youssif).Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, EgyptChemistry Department, Faculty of Science, Minia University, 61519 El-Minia, EgyptIn this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI50 values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI50 = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAFV600E. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAFV600E with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability.http://www.sciencedirect.com/science/article/pii/S1878535223000734UracilThiazolesThiazolidinesAntiproliferativeKinasesDocking |
| spellingShingle | Ashraf A. Aly Mohammed B. Alshammari Akil Ahmad Hesham A. M. Gomaa Bahaa G. M. Youssif Stefan Bräse Mahmoud A. A. Ibrahim Asmaa H. Mohamed Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents Arabian Journal of Chemistry Uracil Thiazoles Thiazolidines Antiproliferative Kinases Docking |
| title | Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents |
| title_full | Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents |
| title_fullStr | Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents |
| title_full_unstemmed | Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents |
| title_short | Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents |
| title_sort | design synthesis docking and mechanistic studies of new thiazolyl thiazolidinylpyrimidine 2 4 dione antiproliferative agents |
| topic | Uracil Thiazoles Thiazolidines Antiproliferative Kinases Docking |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223000734 |
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