Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities
This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, S...
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| Other Authors: | , , , , , |
| Format: | article |
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2017
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| Online Access: | http://hdl.handle.net/10725/5366 http://dx.doi.org/10.1111/cbdd.12929 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12929/full |
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| _version_ | 1864513465842925568 |
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| author | Abd El Razik, Heba A. |
| author2 | Mroueh, Mohamad Faour, Wissam H. Shebaby, Wassim N. Daher, Costantine F. Ashour, Hayam M. A. Ragab, Hanan M. |
| author2_role | author author author author author author |
| author_facet | Abd El Razik, Heba A. Mroueh, Mohamad Faour, Wissam H. Shebaby, Wassim N. Daher, Costantine F. Ashour, Hayam M. A. Ragab, Hanan M. |
| author_role | author |
| dc.creator.none.fl_str_mv | Abd El Razik, Heba A. Mroueh, Mohamad Faour, Wissam H. Shebaby, Wassim N. Daher, Costantine F. Ashour, Hayam M. A. Ragab, Hanan M. |
| dc.date.none.fl_str_mv | 2017-03-14T12:15:18Z 2017-03-14T12:15:18Z 2017 2017-03-14 |
| dc.identifier.none.fl_str_mv | 1747-0277 http://hdl.handle.net/10725/5366 http://dx.doi.org/10.1111/cbdd.12929 Abd El Razik, H. A., Mroueh, M., Faour, W. H., Shebaby, W. N., Daher, C. F., Ashour, H., & Ragab, H. M. (2017). Synthesis of new pyrazolo [3, 4‐d] pyrimidine derivatives and evaluation of their anti‐inflammatory and anticancer activities. Chemical Biology & Drug Design 90 (1), 83-96 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12929/full |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Chemical biology & drug design |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, SF-268, B16F-10) and cyclooxygenase (COX-2) protein expression inhibition in lipopolysaccharide (LPS)-activated rat monocytes. The results revealed that most of the synthesized compounds showed moderate-to-high cytotoxic activity against at least one cell line, with compound 10b being the most active against all used cell lines (IC50 values 5.5–11 μg/ml) comparable to cisplatin. In addition, six of these compounds (7b, 10a–d, and 12c) demonstrated inhibition of LPS-induced COX-2 protein expression at low concentration (25 μg/ml) as compared to the control non-stimulated cells and showed a COX-2 selectivity index range comparable to diclofenac sodium. The overall results indicate that many of these pyrazolopyrimidine derivatives possess in vitro anti-inflammatory and anticancer activities at varying doses, and the most active compounds will be subjected to in vivo pharmacological evaluation. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_3532a31af3fed12d17776cc3fc440ccb |
| identifier_str_mv | 1747-0277 Abd El Razik, H. A., Mroueh, M., Faour, W. H., Shebaby, W. N., Daher, C. F., Ashour, H., & Ragab, H. M. (2017). Synthesis of new pyrazolo [3, 4‐d] pyrimidine derivatives and evaluation of their anti‐inflammatory and anticancer activities. Chemical Biology & Drug Design 90 (1), 83-96 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/5366 |
| publishDate | 2017 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activitiesAbd El Razik, Heba A.Mroueh, MohamadFaour, Wissam H.Shebaby, Wassim N.Daher, Costantine F.Ashour, Hayam M. A.Ragab, Hanan M.This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, SF-268, B16F-10) and cyclooxygenase (COX-2) protein expression inhibition in lipopolysaccharide (LPS)-activated rat monocytes. The results revealed that most of the synthesized compounds showed moderate-to-high cytotoxic activity against at least one cell line, with compound 10b being the most active against all used cell lines (IC50 values 5.5–11 μg/ml) comparable to cisplatin. In addition, six of these compounds (7b, 10a–d, and 12c) demonstrated inhibition of LPS-induced COX-2 protein expression at low concentration (25 μg/ml) as compared to the control non-stimulated cells and showed a COX-2 selectivity index range comparable to diclofenac sodium. The overall results indicate that many of these pyrazolopyrimidine derivatives possess in vitro anti-inflammatory and anticancer activities at varying doses, and the most active compounds will be subjected to in vivo pharmacological evaluation.PublishedN/A2017-03-14T12:15:18Z2017-03-14T12:15:18Z20172017-03-14Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1747-0277http://hdl.handle.net/10725/5366http://dx.doi.org/10.1111/cbdd.12929Abd El Razik, H. A., Mroueh, M., Faour, W. H., Shebaby, W. N., Daher, C. F., Ashour, H., & Ragab, H. M. (2017). Synthesis of new pyrazolo [3, 4‐d] pyrimidine derivatives and evaluation of their anti‐inflammatory and anticancer activities. Chemical Biology & Drug Design 90 (1), 83-96http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://onlinelibrary.wiley.com/doi/10.1111/cbdd.12929/fullenChemical biology & drug designinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/53662024-02-01T12:49:14Z |
| spellingShingle | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities Abd El Razik, Heba A. |
| status_str | publishedVersion |
| title | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| title_full | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| title_fullStr | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| title_full_unstemmed | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| title_short | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| title_sort | Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities |
| url | http://hdl.handle.net/10725/5366 http://dx.doi.org/10.1111/cbdd.12929 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12929/full |