Chemistry Department, Federal University of Espírito Santo, Fernando Ferrari Avenue 514, Vitória 29075-910, ES, Brazil.
Institute of Chemistry, University of Campinas, Josué de Castro Street, Campinas 13083-970, SP, Brazil.
Molecules. 2022 Nov 19;27(22):8051. doi: 10.3390/molecules27228051.
In this work a microwave-assisted Knoevenagel/Michael/cyclization multicomponent domino methodology, using ethanol as solvent and the ionic liquid 1-methylimidazolium chloride as catalyst was developed for the synthesis of spiro compounds. The reaction conditions considered ideal were determined from a methodological study varying solvent, catalyst, amount of catalyst, temperature, and heating mode. Finally, the generality of the methodology was evaluated by exploring the scope of the reaction, varying the starting materials (isatin, malononitrile, and barbituric acid). Overall, the twelve spiro compounds were synthesized in good yields (43-98%) and the X-ray structure of compound was obtained. In addition, the in vitro antiproliferative activities of the spirocycles against four types of human cancer cell lines including HCT116 (human colon carcinoma), PC3 (prostate carcinoma), HL60 (promyelocytic leukemia), and SNB19 (astrocytoma) were screened by MTT-based assay. It is noteworthy that spiro compound inhibited the four cell lines tested with the lowest IC values: 52.81 µM for HCT116, 74.40 µM for PC3, 101 µM for SNB19, and 49.72 µM for HL60.
在这项工作中，我们开发了一种微波辅助的 Knoevenagel/Michael/环化多组分多米诺反应方法，使用乙醇作为溶剂，1-甲基咪唑氯盐作为离子液体催化剂，用于合成螺环化合物。通过改变溶剂、催化剂、催化剂用量、温度和加热方式的方法研究，确定了理想的反应条件。最后，通过探索反应范围，改变起始原料（靛红、丙二腈和巴比妥酸），评估了该方法的通用性。总的来说，12 个螺环化合物以良好的收率（43-98%）合成，并获得了化合物 的 X 射线结构。此外，通过 MTT 基础测定法筛选了螺环化合物对包括 HCT116（人结肠癌细胞）、PC3（前列腺癌细胞）、HL60（早幼粒细胞白血病）和 SNB19（星形细胞瘤）在内的四种人类癌细胞系的体外增殖抑制活性。值得注意的是，螺环化合物 对测试的四种细胞系均具有抑制作用，其最低 IC 值分别为：HCT116 为 52.81 μM，PC3 为 74.40 μM，SNB19 为 101 μM，HL60 为 49.72 μM。
