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Described herein is a facile and efficient methodology toward the synthesis of novel convolutamydine A‐incorporated β‐ionone scaffold 3 from an Aldol addition event of β‐ionone to isatins via enamine Et2NH catalysis. Products featuring a quaternary carbon center were smoothly obtained in good yields (up to 96% yield). This protocol also represents the first construction of ionone skeleton‐fused oxindole molecules, thus leading to new knowledge in the fields of both molecular complexity and diversity‐oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds obtained by this protocol showed comparable with or even much better than the positive control of Cisplatin. [ABSTRACT FROM AUTHOR]

We have developed an efficient and straightforward methodology for the synthesis of novel tanshinone-substituted bis(indolyl/pyrrolyl)methane scaffolds 3 through TsOH catalysis-enabled addition of indoles or pyrroles 1 with tanshinones 2 based on molecular hybridization strategy. Products were smoothly obtained in good yields (up to 81% yield). This protocol also represents the first construction of tanshinone skeleton-fused bis(indolyl/pyrrolyl)methane scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562, human prostate cancer cells PC-3, and human lung cancer cells A549 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds 3 obtained by this protocol showed comparable activity to the positive control of cisplatin. [ABSTRACT FROM AUTHOR]

Reported is a facile and efficient methodology toward the synthesis of novel pyrimidine-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition reaction of pyrimidine-fused 3-alkenyloxindoles 1 with azomethine ylides (thermally generated in situ from sarcosine and formaldehyde). Products bearing adjacent quaternary–tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human lung cancer cells A549, human prostate cancer cells PC-3, and human leukemia cells K562 by the MTT-based assays, using the commercially available broad-spectrum anticancer drug of Cisplatin as a positive control. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines of K562, PC-3, and A549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 3.0 times), and indicated that novel pyrimidine-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules. [ABSTRACT FROM AUTHOR]

Developed herein was an expedient method toward the synthesis of pyrimidine-fused 3-alkenyloxindoles 4 via a Knoevenagel condensation/S N Ar sequential reaction of pyrimidine aldehydes 1 with 2-oxindoles 2 using alcohols 3 as both the solvents and the reactants. A wide variety of products, which is a typical hybridization of two key structural skeletons of 3-alkenyl-oxindole and pyrimidine found in an array of biologically active natural products and pharmaceutical compounds, were obtained smoothly with high efficiency (up to 93% yield) and high ( E/Z )-selectivities (up to >20:1 E/Z ). Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays using the commercially available broad-spectrum anticancer drug Cisplatin as a positive control. These results suggested that most of pyrimidine-fused 3-alkenyloxindoles 4 showed equipotent or more potent than the positive control of Cisplatin (up to 5.1 times), which suggested that pyrimidine-fused 3-alkenyloxindoles 4 may be potential leads for further biological screenings. [ABSTRACT FROM AUTHOR]

A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC 50 = 3.15 ± 0.51 μM), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs. Unlabelled Image • The first example of flavonoid-fused spirooxindoles. • A molecular hybridization strategy. • Compound 3e induced cancer cell apoptosis as a potential anticancer agent. [ABSTRACT FROM AUTHOR]