A cell-based screen for anticancer activity of 13 pyrazolone derivatives  

作　　者：Xiao-Hong Wang Xiao-Kun Wang Yong-Ju Liang Zhi Shi Jian-Ye Zhang Li-Ming Chen Li-Wu Fu 

机构地区：[1]State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer center, Guangzhou, Guangdong 510060, P. R. China

出　　处：《Chinese Journal of Cancer》2010年第12期980-987,共8页

基　　金：National Sciences Foundation (No. 30672407);Key Science and Technology Foundation of Guangdong Province (No. 2004B30101005);No.985-II foundation of State Key Laboratory of Oncology in South China

摘　　要：Background and Objective: Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed. Methods: To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells. Results: Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively. Conclusion: Compound 9 was the most promising antitumor agent in this study.Background and Objective： Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance （MDR） KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed. Methods： To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration （IC50） values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells. Results： Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were （3.24 ± 0.28）, （2.58 ± 0.61）, （3.81 ± 0.02）, and （3.45 ± 0.03） μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively （P 0.05）. Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively. Conclusion： Compound 9 was the most promising antitumor agent in this study.

关 键 词：吡唑啉酮 酮衍生物 抗癌活性 合成化合物 肿瘤细胞株 细胞毒性 屏幕 单元 

分 类 号：Q959.133[生物学—动物学] O626.21[理学—有机化学]