6-氯／甲基-2／3-芳基取代喹喔啉衍生物的合成及抗肿瘤活性研究

摘要

Objective Synthesis and anti‐tumor activity of 6‐chloro/methyl‐2/3‐arylquinoxaline derivatives on SGC‐7901 and HepG2 cells have been studied . Methods Target compounds(3c‐1~7m‐1) were synthesized by cyclization ,chlorination ,and nucleophilic substitution reactionwith 4‐chloro/methyl‐benzene‐1 ,2‐diamine and 1 ,2‐dione compounds(diethyl oxalate) as the starting materials . The antitumor activity of 15 new compounds was evaluated by MTT assay . Results Target compounds can be synthe‐sized and all of them were further characterized by IR and 1 H NMR . The results showed that the inhibi‐ting rate of target compounds on SGC‐7901 was greater than that of them on HepG2 cells ,and inhibition effect of 6‐chloro‐2/3‐arylquinoxaline derivatives to SGC‐7901 cells was better than that of 6‐methyl‐2/3‐arylquinoxaline derivatives . T he inhibiting rate of 6‐chloro‐2/3‐arylquinoxaline derivatives (5c‐1 ) and 6‐methyl‐2/3‐arylquinoxaline derivatives (7m‐1) was 2 .02 and 0 .001 6 μg/mL ,respectively . Conclusion Anti‐tumor activity of target compounds(5c‐1 ,7m‐1) on SGC‐7901 was good . Therefore ,the struc‐ture of 6‐chloro/methyl‐2/3‐arylquinoxaline derivatives can be optimized to promote the anticancer activity of quinoxaline derivatives .%目的：合成6‐氯／甲基‐2／3‐芳基喹喔啉衍生物，并测试其对SGC‐7901和HepG2肿瘤细胞增殖的抑制作用。方法以4‐氯／甲基邻苯二胺为起始原料，通过与草酸二乙酯环合、氯代、亲核取代反应合成6‐氯／甲基‐2／3‐芳基喹喔啉衍生物（3c‐1～7m‐1），并用M T T法测试所得目标化合物的抗肿瘤活性。结果合成得到15个相应的目标化合物，通过IR和1 H NMR确认结构。此类化合物对SGC‐7901肿瘤细胞增殖抑制作用较 HepG2细胞强，6‐氯‐2／3‐芳基喹喔啉衍生物抗肿瘤活性多数大于6‐甲基‐2／3‐芳基喹喔啉衍生物。6‐氯‐2／3‐芳基喹喔啉衍生物（5c‐1）和6‐甲基‐2／3‐芳基喹喔啉衍生物（7m‐1）对 SGC‐7901细胞增殖抑制 IC50值分别为2．02和0．0016μg／mL。结论目标产物（5c‐1，7m‐1）对SGC‐7901肿瘤细胞增殖抑制活性好，可以进行结构优化，以期开发毒副作用小、耐受性好的新型抗肿瘤药物。