Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
Guangxi Key Laboratory Cultivation Base of AIDS Prevention and Treatment, Guangxi Medical University, Nanning, China.
Chem Biol Drug Des. 2018 Apr;91(4):957-961. doi: 10.1111/cbdd.13154. Epub 2018 Jan 20.
A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized by introducing benzyl ether, benzoate, and benzenesulfonate to 6-position of furo[2,3-b]quinoline and their chemical structures were confirmed by ESI-MS, H NMR, and C NMR spectra. All target compounds were evaluated in vitro against four human cancer cell lines (HCT-116, MCF-7, U2OS, and A549) by MTT method. Cytotoxic assay showed that compounds 8a, 8e, 10a, 10b, and 10c exhibited more potent cytotoxicities compared to 2-bromine-6-hydroxy-furo-[2,3-b]quinoline (7). Compound 10c exhibited higher antiproliferative activity (IC values ranging from 4.32 to 24.96 μm) against four human cancer cell lines (HCT-116, MCF-7, U2OS, and A549) and weak cytotoxicity on normal cell HL-7702, which suggested that 10c might be an ideal anticancer candidate. Compounds 8a, 10a, 10b showed good selectivities to MCF-7 and HCT-116, which could be considered as ideal selective candidates for further study. The SARs showed that the introduction of the benzyl ether and benzenesulfonate could significantly improve cytotoxicities, while the benzoate failed to enhance potency obviously.
设计并合成了一系列新型呋喃并[2,3-b]喹啉衍生物，通过在呋喃并[2,3-b]喹啉的 6-位引入苄醚、苯甲酸酯和苯磺酸盐，通过 ESI-MS、1H NMR 和 13C NMR 光谱确认了它们的化学结构。通过 MTT 法，对所有目标化合物在体外对四种人癌细胞系（HCT-116、MCF-7、U2OS 和 A549）进行了评估。细胞毒性试验表明，与 2-溴-6-羟基呋喃并[2,3-b]喹啉（7）相比，化合物 8a、8e、10a、10b 和 10c 表现出更强的细胞毒性。化合物 10c 对四种人癌细胞系（HCT-116、MCF-7、U2OS 和 A549）具有更高的增殖抑制活性（IC 值范围为 4.32 至 24.96 μm），对正常细胞 HL-7702 的细胞毒性较弱，这表明 10c 可能是一种理想的抗癌候选药物。化合物 8a、10a 和 10b 对 MCF-7 和 HCT-116 具有良好的选择性，可被视为进一步研究的理想选择性候选药物。SAR 表明，引入苄醚和苯磺酸盐可显著提高细胞毒性，而苯甲酸酯未能明显增强其活性。
