Molecular hybridization-guided 1,3-dipolar cycloaddition reaction enabled pyrimidine-fused spiropyrrolidine oxindoles synthesis as potential anticancer agents.

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]