Abstract Novel pyrrole derivatives were synthesized by one-pot four components condensation reaction of khellin and/or visnagin carbaldehyde; amine derivatives; curcumin and nitro methane. In another approach with lack of curcumin molecular structure, new pyrrole derivatives were efficiently achieved using ethyl acetoacetate. Newly synthesized compounds were tested against human pancreas cancer cell lines (Panc-1), colon cancer cell line and (MCF-7), (HT-29) breast cancer cell line. The results showed that newly synthesized compounds exhibit a moderate to strong growth inhibition of breast cancer cell line MCF-7 in comparison to the other two cell lines. Compounds which are combination between both Curcumin and khelline derivatives showed highest activity towards human breast cancer cell line (MCF-7). Molecular docking studies declared that these compounds occupied a pocket of “EGFR tyrosine kinase” (WT) and a pocket of “EGFAR Kinase domain PCSK9-∆C D374Y” (MT). In addition, our compounds are non-inhibitors of CYP2D6, which means that liver dysfunction effects are not expected. All newly synthesized strucrures are consistent with biological results and predicted to be safe.

中文翻译：

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Khellin 和 Visnagin 新型吡咯衍生物与姜黄素的一锅缩合反应的合成、细胞毒性评价和分子对接研究

摘要 通过海林碱和/或内酯甲醛的一锅四组分缩合反应合成了新型吡咯衍生物；胺衍生物；姜黄素和硝基甲烷。在另一种缺乏姜黄素分子结构的方法中，使用乙酰乙酸乙酯有效地获得了新的吡咯衍生物。新合成的化合物针对人胰腺癌细胞系 (Panc-1)、结肠癌细胞系和 (MCF-7)、(HT-29) 乳腺癌细胞系进行了测试。结果表明，与其他两种细胞系相比，新合成的化合物对乳腺癌细胞系 MCF-7 具有中度至强的生长抑制作用。姜黄素和 khelline 衍生物组合的化合物对人乳腺癌细胞系 (MCF-7) 显示出最高的活性。分子对接研究表明，这些化合物占据了一个“EGFR酪氨酸激酶”（WT）口袋和一个“EGFAR激酶域PCSK9-ΔC D374Y”（MT）口袋。此外，我们的化合物是 CYP2D6 的非抑制剂，这意味着不会对肝功能障碍产生影响。所有新合成的结构都与生物学结果一致，预测是安全的。