Motamedi Radineh, Shafiee Abbas, Rezai Mohammad Reza, Firuzi Omidreza, Edraki Najmeh, Miri Ramin
Department of Chemistry, Payame Noor University, Delijan, Iran.
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
Iran J Pharm Res. 2014 Winter;13(1):103-14.
In the present work, novel 7-aryl-10, 11-dihydro-7H-chromeno [4, 3-b]quinoline-6, 8(9H, 12H)-dione derivatives were synthesized by oxidation of 7-aryl-8, 9, 10, 12-tetrahydro-7H-chromeno[4, 3-b]quinoline-6, 8-diones in the presence of silica sulfuric acid/NaNO2 with yields of 64-74%. Cytotoxic activity of synthesized compounds was assessed on three different human cancer cell lines (K562, LS180, and MCF-7). Synthesized compounds showed moderate cytotoxic activities. The most active one apeared to be 2e, containing a methoxy group on the meta position of phenyl ring (IC50 range in different cell lines: 11.1-55.7 µM). Furthermore; comparison of the cytotoxic activity of these novel oxidized derivatives with non-oxidized counterparts revealed that oxidation of dihydropyridine ring to pyridine, improves the activity especially in LS180 cell line. Conformational analysis revealed that some conformational aspects of oxidized derivatives such as orientation of C7-aryl substitute were clearly different from non-oxidized ones.
在本研究中，通过在硅胶硫酸/亚硝酸钠存在下氧化7-芳基-8,9,10,12-四氢-7H-色烯并[4,3-b]喹啉-6,8-二酮，合成了新型7-芳基-10,11-二氢-7H-色烯并[4,3-b]喹啉-6,8(9H,12H)-二酮衍生物，产率为64-74%。在三种不同的人类癌细胞系（K562、LS180和MCF-7）上评估了合成化合物的细胞毒性活性。合成化合物显示出中等的细胞毒性活性。活性最高的似乎是2e，其在苯环间位含有一个甲氧基（在不同细胞系中的IC50范围：11.1-55.7μM）。此外，将这些新型氧化衍生物与未氧化的对应物的细胞毒性活性进行比较，发现二氢吡啶环氧化为吡啶可提高活性，尤其是在LS180细胞系中。构象分析表明，氧化衍生物的一些构象方面，如C7-芳基取代基的取向，与未氧化的衍生物明显不同。
