Dawood Dina H, Abbas Eman M H, Farghaly Thoraya A, Ali Mamdouh M, Ibrahim Mohammed F
Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Center, 33 El Bohouth St.( former El Tahrir St.) Dokki, Giza, P.O. Box 12622, Egypt.
Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Med Chem. 2019;15(3):277-286. doi: 10.2174/1573406414666180912113226.
Pyrimidines emerged as a remarkable class of heterocyclic compounds that have reinforced the pharmaceutical chemistry with various bioactive antitumor agents. Moreover, pyrimidine scaffold displayed VEGFR-2 inhibitory activity. Also, nano-sized catalysts are used in organic reactions in order to speed up the catalytic process.
We were interested herein to synthesize a new series of fused pyrimidines using ZnO(NPs) to investigate their antitumor efficiency against breast MCF7 cancer and their VEGFR- 2 inhibition properties.
A simple and efficient method for the synthesis of fused pyrimidines was developed using zinc oxide nanoparticles ZnO(NPs) in refluxing ethanol.
The proposed structures of all new fused pyrimidines are in agreement with their spectral data. Antitumor evaluation of newly fused pyrimidine derivatives against breast MCF-7 cancer was performed. It was apparent that the 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a (IC50 = 9.12±1.16 µg/ml), 9c (IC50 = 9.10±1.07 µg/ml) and 9d (IC50 = 9.60±1.22 µg/ml) exhibited equipotent antitumor activity as Tamoxifen (IC50 = 9.11±0.90 µg/ml). Also, the inhibitory activity of the novel fused pyrimidine derivatives on VEGFR-2 as well as Tamoxifen was determined using breast cancer cell line MCF-7. The data was obvious that 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a, 9c and 9d exhibited noticeable VEGFR-2 inhibitory effect with % inhibition ranging from 80-84 % versus Tamoxifen 93.5%.
We succeeded in this context to synthesize new fused pyrimidines using ZnO(NPs) as anti-breast cancer agents targeting VEGFR-2.
嘧啶作为一类重要的杂环化合物，凭借多种具有生物活性的抗肿瘤药物，为药物化学领域增添了光彩。此外，嘧啶骨架展现出血管内皮生长因子受体2（VEGFR - 2）抑制活性。同时，纳米尺寸的催化剂被应用于有机反应中，以加速催化过程。
我们在此有兴趣利用氧化锌纳米颗粒（ZnO(NPs)）合成一系列新型稠合嘧啶，以研究它们对乳腺癌MCF7细胞的抗肿瘤效果及其VEGFR - 2抑制特性。
开发了一种简单高效的方法，即在回流乙醇中使用氧化锌纳米颗粒（ZnO(NPs)）合成稠合嘧啶。
所有新型稠合嘧啶的推测结构与其光谱数据相符。对新合成的稠合嘧啶衍生物进行了抗乳腺癌MCF - 7细胞的抗肿瘤评估。显然，2 - 苯基吡唑并[1,5 - a]嘧啶衍生物9a（半数抑制浓度（IC50）= 9.12±1.16微克/毫升）、9c（IC50 = 9.10±1.07微克/毫升）和9d（IC50 = 9.60±1.22微克/毫升）表现出与他莫昔芬（IC50 = 9.11±0.90微克/毫升）相当的抗肿瘤活性。此外，使用乳腺癌细胞系MCF - 7测定了新型稠合嘧啶衍生物以及他莫昔芬对VEGFR - 2的抑制活性。数据表明，2 - 苯基吡唑并[1,5 - a]嘧啶衍生物9a、9c和9d表现出显著的VEGFR - 2抑制作用，抑制率在80 - 84%之间，而他莫昔芬为93.5%。
在这方面，我们成功利用ZnO(NPs)合成了新型稠合嘧啶，作为靶向VEGFR - 2的抗乳腺癌药物。
