Division of Organic and Biomolecular Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad 500 067, India.
Bioorg Med Chem Lett. 2013 Jul 15;23(14):4061-6. doi: 10.1016/j.bmcl.2013.05.060. Epub 2013 May 29.
New cis-fused chromeno pyrano[4,3-c]isoxazole derivatives have been synthesized by intramolecular [1,3]-cycloaddition of the nitrones generated in situ from hydroxylamine derivatives and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones using PEG-400 as a reaction medium under catalyst-free conditions good to excellent yields. The structures were established by spectroscopic data and further confirmed by X-ray diffraction analysis. The results showed that compounds 4b, 4c, 4d, 4e and 4k exhibit very potent antiproliferative activity against MDA-MB-231 breast cancer cells. Compounds 4a, 4c, 4e, 4i and 4k displayed potent inhibitory activity against human MCF-7 breast cancer cell lines. Compounds 4h and 4i exhibited significant anti-proliferative activity against human cervical cancer cell line, HeLa. While 4b, 4d and 4j were active against human lung cancer cell line, A549. In addition, Compound 4j was found to be the most promising against A549 (Lung cancer) with IC50 value of 0.194 μM.
新的顺式稠合色烯并[4,3-c]异噁唑衍生物已经通过羟胺衍生物和 7-O-异戊烯基取代的 8-甲酰基-2,3-二取代色烯酮的原位生成的硝酮的分子内环加成，在无催化剂条件下，以聚乙二醇 400 作为反应介质，以良好至优异的收率得到合成。结构通过光谱数据建立，并通过 X 射线衍射分析进一步证实。结果表明，化合物 4b、4c、4d、4e 和 4k 对 MDA-MB-231 乳腺癌细胞表现出非常强的抗增殖活性。化合物 4a、4c、4e、4i 和 4k 对人 MCF-7 乳腺癌细胞系显示出很强的抑制活性。化合物 4h 和 4i 对人宫颈癌细胞系 HeLa 表现出显著的抗增殖活性。而 4b、4d 和 4j 对人肺癌细胞系 A549 具有活性。此外，化合物 4j 对 A549（肺癌）的活性最强，IC50 值为 0.194 μM。
