Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
National Organization for Drug Control and Research (NODCAR) P.O. 29, Cairo, Egypt.
Anticancer Agents Med Chem. 2021;21(17):2443-2463. doi: 10.2174/1871520621666210112115128.
Recently, products of Multi-Component Reactions (MCR's) acquired special attention due to their wide range of pharmacological activities especially therapeutic activities. In the market it was found that many pharmacological drugs containing the pyran and pyridine nucleus that were produced through MCR's were found.
This work aims to synthesize target molecules not only possess anti-tumour activities but also c-Met and prostate cancer inhibitors. The target molecules were obtained starting from cyclohexan-1,3-dione through its multi-component reactions to produce anticancer target molecules.
Cyclohexane-1,3-dione underwent different multi-component reactions to produce fused pyran, pyridine and thiophene derivatives. The anti-proliferative activity of the newly synthesized compounds among the synthesized compounds toward the six cancer cell lines, namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition, inhibitions toward c-Met kinase and prostate cancer cell line were studied. Antitumor evaluations toward seventeen cancer cell lines subpanel, for certain compounds, were also demonstrated according to the diseases. Pim-1 kinase inhibitions of the most active compounds were also measured.
Anti-proliferative evaluations, c-Met and Pim-1 kinase inhibitions were performed for most of the synthesized compounds where the varieties of substituent through the aryl ring and the heterocyclic ring afforded compounds with high activities.
Compounds 4b, 6b, 8b, 9a, 11b, 12b, 17b, 18b, 19, 22c, 23b, 25b and 26b were the most cytotoxic compounds toward the six cancer cell lines. Inhibitions toward c-Met kinase and prostate cancer cells showed that the presence of the electronegative Cl group within the molecule were responsible for its high activity. In addition, inhibitions toward Pim-1 kinase exhibited that most of tested compounds showed high inhibitions.
最近，多组分反应（MCR）的产物由于其广泛的药理活性，尤其是治疗活性，引起了特别的关注。在市场上发现，许多含有吡喃和吡啶核的药理药物都是通过 MCR 生产的。
本工作旨在合成不仅具有抗肿瘤活性，而且还具有 c-Met 和前列腺癌抑制剂活性的靶分子。从环己-1,3-二酮出发，通过多组分反应得到抗癌靶分子，从而获得目标分子。
环己-1,3-二酮经历不同的多组分反应，生成稠合的吡喃、吡啶和噻吩衍生物。研究了新合成化合物对六种癌细胞系，即 A549、H460、HT-29、MKN-45、U87MG 和 SMMC-7721 的增殖抑制活性。此外，还研究了对 c-Met 激酶和前列腺癌细胞系的抑制作用。根据疾病，还对某些化合物进行了 17 种癌症细胞系亚组的抗肿瘤评估。还测量了最活跃的化合物对 Pim-1 激酶的抑制作用。
对大多数合成化合物进行了增殖抑制评价、c-Met 和 Pim-1 激酶抑制评价，其中通过芳基环和杂环的取代基变化提供了具有高活性的化合物。
化合物 4b、6b、8b、9a、11b、12b、17b、18b、19、22c、23b、25b 和 26b 是对六种癌细胞系最具细胞毒性的化合物。对 c-Met 激酶和前列腺癌细胞的抑制作用表明，分子内存在吸电子 Cl 基团是其高活性的原因。此外，对 Pim-1 激酶的抑制作用表明，大多数测试化合物表现出高抑制作用。
