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目的寻找氟喹诺酮C-3羧基等排体噁二唑的修饰方法,提高其衍生物的抗肿瘤活性。方法基于药效团与骨架跃迁原理,用功能基侧链硫乙酰腙类作为C-3等排体的修饰基团,设计合成了氟喹诺酮C-3噁二唑硫乙酰腙目标化合物。用MTT方法评价了目标化合物对体外培养肿瘤细胞的生长抑制活性。结果合成14个目标化合物,体外均显示潜在的抗肿瘤活性,尤其是修饰基含有羧基取代苯环的化合物其抗肿瘤活性与多柔比星的活性相当。结论吸电子基酰腙作为C-3等排体的修饰基团值得关注。
OBJECTIVE: To search for the modification method of fluoroquinolone C-3 carboxyl isostere oxadiazole to improve the antitumor activity of its derivatives. Methods A fluoroquinolone C-3 oxadiazolethioacetyl hydrazone compound was designed and synthesized based on the theory of pharmacophore and framework transition. The functional group-based side-chain thioacetyl hydrazones were used as modifying groups of C-3 isosteres. The growth inhibitory activity of the target compound on cultured tumor cells was evaluated by MTT method. Results The 14 target compounds were synthesized and showed potential antitumor activity in vitro. Especially, the compounds with carboxyl-substituted benzene ring in the modification showed antitumor activity comparable to that of doxorubicin. Conclusions Electron-absorbing acylhydrazone is the focus of C-3 isostere modification group.