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目的寻找转化抗菌氟喹诺酮到抗肿瘤氟喹诺酮的有效策略。方法用酰腙作为恩诺沙星1C3羧基的生物电子等排体,合成了12个新的恩诺沙星酰腙(3a-3l)目标化合物,其结构经元素分析和光谱数据确证。用MTT方法评价了目标化合物体外对SMMC-7721、L1210和HL60 3种癌细胞的生长抑制活性。结果酰腙目标物对3种实验癌细胞的生长抑制活性显著强于母体化合物1,苯环带吸电子化合物的活性强于供电子化合物的活性,尤其对肝癌SMMC-7721细胞的活性明显高于对白血病细胞L1210和HL60的活性。结论氟喹诺酮羧基并非是抗肿瘤活性所必需的药效团,其被酰腙取代可显著提高其抗肿瘤活性。
Objective To search for an effective strategy for transforming antifungal fluoroquinolones into antifumor fluoroquinolones. Methods The acyl hydrazone was used as the bioisostere of the enrofloxacin 1C3 carboxyl group. Twelve novel target compounds of enrofloxacin hydrazone (3a-3l) were synthesized and their structures were confirmed by elemental analysis and spectral data. The inhibitory activity of the target compounds on the growth of SMMC-7721, L1210 and HL60 cancer cells in vitro was evaluated by MTT method. Results The inhibitory activity of acylhydrazone on the growth of SMMC-7721 cells was significantly higher than that of the parent compound 1, and the activity of benzene ring compounds with electron-withdrawing compounds was stronger than that of electron-donor compounds. Leukemia cells L1210 and HL60 activity. Conclusion The fluoroquinolone carboxyl group is not a necessary pharmacophore for antitumor activity. Substitution of acyl hydrazone by acylhydrazone can significantly enhance its anti-tumor activity.