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...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Abd El Razik, Heba A. (author)
مؤلفون آخرون: Mroueh, Mohamad (author), Faour, Wissam H. (author), Shebaby, Wassim N. (author), Daher, Costantine F. (author), Ashour, Hayam M. A. (author), Ragab, Hanan M. (author)
التنسيق: article
منشور في: 2017
الوصول للمادة أونلاين: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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الوصف
الملخص: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.