引入了一种新型高效的无可见光促进催化剂(VLCF)策略,用于纯净和清洁地合成螺吲哚并-喹唑啉酮-吡咯并[3,4-a]吡咯烷杂化物(6a-d)。我们已经进行了马来酰亚胺(5a-d)与由色胺酮(3)和L-脯氨酸(4)原位产生的甲亚胺叶立德的可见光触发的1,3-偶极环加成反应,以良好至优异的收率获得所需的产物(6a-d)。使用各种光谱技术,如IR,1HNMR,13CNMR,质谱和单晶XRD剖析。为了解释反应自发性,产品稳定性,反应性以及相互作用的可能模式进行了量子化学研究,并通过DFT研究进行了描述。还评估了合成的化合物6a对一组五种癌细胞系(MCF-7,MDA-MB-231,HeLa,PC-3和Ishikawa)和正常人胚肾(HEK-293)细胞系,使用MTT测定法。化合物6a对四种癌细胞系显示出非常好的体外抗增殖活性(IC50=6.58-17.98μM),并且对正常HEK-293没有细胞毒性。为了评估化合物6a-d的抗癌潜力,针对野生型和突变型EGFR进行分子对接.结果表明,所有化合物都占据了两种酶的活性位点,具有强结合能(-10.2至-11.5kcal/mol)。通过评估均方根偏差(RMSD)和均方根波动(RMSF),分子动力学模拟证实了这些结果。以及主成分分析(PCA)。由RamaswamyH.Sarma沟通。
A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50 = 6.58-17.98 μM) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma.