Synthesis and in vitro evaluation of pyrimidine-fused 3-alkenyloxindoles as potential anticancer agents

Developed herein was an expedient method toward the synthesis of pyrimidine-fused 3-alkenyloxindoles 4 via a Knoevenagel condensation/SNAr 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. (C) 2016 Elsevier Ltd. All rights reserved.