Natural Products Laboratory, Department of Chemistry, Osmania University, Hyderabad, Telangana, India.
Department of Genetics and Biotechnology, Osmania University, Hyderabad, Telangana, India.
Arch Pharm (Weinheim). 2020 Jun;353(6):e2000006. doi: 10.1002/ardp.202000006. Epub 2020 Apr 20.
A series of new benzofuran/oxadiazole hybrids (8a-n) was synthesized from 2H-chromene-3-carbonitriles (3a-c) through the multistep synthetic methodology, and these hybrids are known to exhibit anticancer activities. All the compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Compounds 6a (IC : 9.71 ± 1.9 μM), 6b (IC : 7.48 ± 0.6 μM), and 6c (IC : 3.27 ± 1.1 μM) displayed a significant cytotoxic activity, whereas compounds 8d and 8e exhibited good activity against both cell lines. The depletion of glycogen synthase kinase-3β (GSK3β) induces apoptosis through the inhibition of basal NF-κB activity in HCT116 colon cancer cells and MIA PaCa2 pancreatic cancer cells. Molecular docking of compounds 6a, 6b, 6c, 8d, and 8e with GSK3β demonstrated the best binding affinity, correlating with the biological activity assay. Furthermore, the structure-activity relationship of these novel compounds reveals promising features for their use in anticancer therapy.
一系列新的苯并呋喃/恶二唑杂合化合物（8a-n）是通过多步合成方法从 2H-色烯-3-氰基化合物（3a-c）合成的，这些杂合化合物已知具有抗癌活性。所有化合物均在体外对 HCT116 和 MIA PaCa2 细胞系进行了细胞毒性评估。化合物 6a（IC：9.71±1.9μM）、6b（IC：7.48±0.6μM）和 6c（IC：3.27±1.1μM）表现出显著的细胞毒性活性，而化合物 8d 和 8e 对两种细胞系均表现出良好的活性。糖原合酶激酶-3β（GSK3β）的耗竭通过抑制 HCT116 结肠癌细胞和 MIA PaCa2 胰腺癌细胞中 NF-κB 的基础活性诱导细胞凋亡。化合物 6a、6b、6c、8d 和 8e 与 GSK3β 的分子对接显示出最佳的结合亲和力，与生物活性测定相关。此外，这些新型化合物的构效关系揭示了它们在癌症治疗中的应用具有有希望的特征。
