Ghosh Rajat, Vitor Jorge B, Mendes Eduarda, Paulo Alexandra, Acharya Pratap Chandra
Department of Pharmacy, Tripura University, Suryamaninagar, Agartala 799022, India.
Faculty of Pharmacy, University of Lisbon, Av Prof Gama Pinto, Lisbon 1649-003, Portugal.
ACS Omega. 2020 Oct 16;5(42):27332-27343. doi: 10.1021/acsomega.0c03675. eCollection 2020 Oct 27.
A highly stereoselective, one-pot, multicomponent method has been developed to synthesize pyrrolizidine- and -methyl pyrrolidine-substituted spirooxindole derivatives. The [3 + 2] cycloaddition reaction involves the reaction between the dipole azomethine ylides, generated from the reaction between isatin and secondary amino acids such as L-proline or sarcosine, and α,β-unsaturated carbonyl compounds as the dipolarophile. The reaction condition was optimized to achieve excellent regio- and stereoselectivity. Products were obtained in good yield using ethanol as a solvent at the reflux temperature. The newly synthesized spirooxindole derivatives were evaluated for their antiproliferative efficacy against National Cancer Institute (NCI)-60 cancer cell lines and DNA G-quadruplex (G4) interaction capacity. Compound produced selective cytotoxicity against leukemia, renal, colon, and prostate cancer cell lines at a 10 μM concentration. The G4 interaction studies further suggested that these spirooxindole derivatives were devoid of any activity as DNA G4 ligands.
已开发出一种高度立体选择性的一锅多组分方法来合成吡咯里西啶和甲基吡咯烷取代的螺环氧化吲哚衍生物。[3 + 2]环加成反应涉及由异吲哚酮与L-脯氨酸或肌氨酸等仲氨基酸反应生成的偶极甲亚胺叶立德与作为亲偶极体的α,β-不饱和羰基化合物之间的反应。对反应条件进行了优化，以实现优异的区域和立体选择性。以乙醇为溶剂，在回流温度下以良好的产率获得了产物。对新合成的螺环氧化吲哚衍生物针对美国国立癌症研究所（NCI）-60癌细胞系的抗增殖功效和DNA G-四链体（G4）相互作用能力进行了评估。化合物在10 μM浓度下对白血病、肾、结肠和前列腺癌细胞系产生了选择性细胞毒性。G4相互作用研究进一步表明，这些螺环氧化吲哚衍生物作为DNA G4配体没有任何活性。
