Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity, Medicinal Chemistry and Natural Products (LR11ES39), Faculty of Sciences Monastir, University of Monastir, Monastir 5000, Tunisia.
Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
Int J Mol Sci. 2021 Sep 23;22(19):10258. doi: 10.3390/ijms221910258.
To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-]pyrido[1,2-]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV-Vis, H NMR, C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.
为了探索一组新的抗癌剂，我们设计并合成了一系列新型吡唑并[4,3-]吡啶并[1,2-]嘧啶衍生物，方法是通过吡唑烯胺与一系列芳基亚甲基丙二腈的环缩合反应；化合物 是由 5-氨基-4-氰基吡唑获得的。通过光谱技术和元素分析（IR、UV-Vis、H NMR、C NMR 和 ESI-MS）研究了目标化合物的结构。使用不同的人肿瘤细胞系 A375、HT29、MCF7、A2780、FaDu 以及非恶性 NIH 3T3 和 HEK293 细胞，评估了所有化合物的体外细胞毒性。结果发现，带有 4-Br-苯基部分的吡唑并-吡啶并嘧啶类似物对许多细胞系最具活性，EC 值在 9.1 和 13.5 µM 之间。此外，还对后者与六种抗癌药物靶点（DHFR、VEGFR2、HER-2/neu、hCA-IX、CDK6 和 LOX5）进行了计算机对接研究，以深入了解其可能的结合作用方式，并估算该生物活性分子的自由结合能。
