Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues
The reaction of 3-amino-5-phenylaminopyrazoles 2 with 3-(dimethylamino) acrylonitrile derivatives resulted in a series of substituted pyrazolopyrimidine analogues 4 and 6. The DFT studies of the isolated compounds showed that the frontier molecular orbitals energy gap was close and in the 2.65–2.81 ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222007535 |
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| author | Omer A. Azher Aisha Hossan Rami A. Pashameah Amerah Alsoliemy Arwa Alharbi Turki M. Habeebullah Nashwa M. El-Metwaly |
| author_facet | Omer A. Azher Aisha Hossan Rami A. Pashameah Amerah Alsoliemy Arwa Alharbi Turki M. Habeebullah Nashwa M. El-Metwaly |
| author_sort | Omer A. Azher |
| collection | DOAJ |
| description | The reaction of 3-amino-5-phenylaminopyrazoles 2 with 3-(dimethylamino) acrylonitrile derivatives resulted in a series of substituted pyrazolopyrimidine analogues 4 and 6. The DFT studies of the isolated compounds showed that the frontier molecular orbitals energy gap was close and in the 2.65–2.81 eV range where the derivative 6b has the lowest and both of 4a and 4c have the highest values. Meanwhile, the anticancer activity of the newly synthesized pyrazolopyrimidine analogues have been tested against several different cell lines (MCF-7, PC3, Hep-2 and WI38). The investigated pyrazolopyrimidines showed remarkable cytotoxicity activity against the MCF-7 and Hep-2 cell lines. In comparison to the effects of 5-fluorouracil, IC50 = 10.19 ± 0.42 and 7.19 ± 0.47, compounds 6a-c demonstrated potential anticancer activity with IC50 values for MCF-7 (10.80 ± 0.36–19.84 ± 0.49 μM) and Hep-2 (8.85 ± 0.24–12.76 ± 0.16 μM). Important details regarding the protein's binding sites were disclosed when the produced analogues docked with the crystal structure of the KDM5A protein, which was located in the protein data library. |
| first_indexed | 2024-04-11T14:08:04Z |
| format | Article |
| id | doaj.art-692f3c1063914b1c8c4efcadf40f2e11 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-11T14:08:04Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-692f3c1063914b1c8c4efcadf40f2e112022-12-22T04:19:49ZengElsevierArabian Journal of Chemistry1878-53522023-01-01161104437Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analoguesOmer A. Azher0Aisha Hossan1Rami A. Pashameah2Amerah Alsoliemy3Arwa Alharbi4Turki M. Habeebullah5Nashwa M. El-Metwaly6Department of laboratory Medicine, Faculty of Applied Biomedical Sciences, Al-Baha University, Saudi ArabiaDepartment of Chemistry, Faculty of science, King Khalid University, Abha, Saudi ArabiaDepartment of Chemistry, Faculty of Applied Science, Umm Al Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, Faculty of Applied Science, Umm Al Qura University, Makkah 24230, Saudi ArabiaDepartment of Chemistry, Faculty of Applied Science, Umm Al Qura University, Makkah 24230, Saudi ArabiaDepartment of Environment and Health Research, The Custodian of the two holy mosques Institute for Hajj and Umrah Research, Umm Al Qura University, Makkah, Saudi ArabiaDepartment of Chemistry, Faculty of Applied Science, Umm Al Qura University, Makkah 24230, Saudi Arabia; Department of Chemistry, Faculty of Science, Mansoura University, El-Gomhoria Street 35516, Egypt; Corresponding author.The reaction of 3-amino-5-phenylaminopyrazoles 2 with 3-(dimethylamino) acrylonitrile derivatives resulted in a series of substituted pyrazolopyrimidine analogues 4 and 6. The DFT studies of the isolated compounds showed that the frontier molecular orbitals energy gap was close and in the 2.65–2.81 eV range where the derivative 6b has the lowest and both of 4a and 4c have the highest values. Meanwhile, the anticancer activity of the newly synthesized pyrazolopyrimidine analogues have been tested against several different cell lines (MCF-7, PC3, Hep-2 and WI38). The investigated pyrazolopyrimidines showed remarkable cytotoxicity activity against the MCF-7 and Hep-2 cell lines. In comparison to the effects of 5-fluorouracil, IC50 = 10.19 ± 0.42 and 7.19 ± 0.47, compounds 6a-c demonstrated potential anticancer activity with IC50 values for MCF-7 (10.80 ± 0.36–19.84 ± 0.49 μM) and Hep-2 (8.85 ± 0.24–12.76 ± 0.16 μM). Important details regarding the protein's binding sites were disclosed when the produced analogues docked with the crystal structure of the KDM5A protein, which was located in the protein data library.http://www.sciencedirect.com/science/article/pii/S18785352220075353-aminopyrazolesPyrazolopyrimidinesMolecular modellingMCF-7Molecular docking |
| spellingShingle | Omer A. Azher Aisha Hossan Rami A. Pashameah Amerah Alsoliemy Arwa Alharbi Turki M. Habeebullah Nashwa M. El-Metwaly Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues Arabian Journal of Chemistry 3-aminopyrazoles Pyrazolopyrimidines Molecular modelling MCF-7 Molecular docking |
| title | Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues |
| title_full | Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues |
| title_fullStr | Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues |
| title_full_unstemmed | Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues |
| title_short | Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo[1,5-a]pyrimidine analogues |
| title_sort | synthesis anticancer evaluation and molecular modeling study of new 2 phenylamino pyrazolo 1 5 a pyrimidine analogues |
| topic | 3-aminopyrazoles Pyrazolopyrimidines Molecular modelling MCF-7 Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222007535 |
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