Synthesis, anticancer evaluation and docking study of vadimezan derivatives with carboxyl substitution

• Published in: MedChemComm 2014, Vol.5 (4), p.512-520
• Main Authors: Zhang, Shi-Jie, Ding, Zhi-Shan, Jiang, Fu-Sheng, Ge, Qiu-Fu, Guo, Dian-Wu, Li, Hai-Bo, Hu, Wei-Xiao
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/C3MD00372H

A series of xanthone analogues modified from vadimezan 6 with carboxyl substitution were synthesized as esters, amides, arylidene hydrazides, diacylhydrazides and acyl thiosemicarbazides, and their structures were confirmed by IR, 1 H NMR, MS, HRMS or elemental analysis. The in vitro anticancer activities were evaluated by the MTT method. It was found that compounds 8f , 8g and 10e were effective against A549 with an IC 50 at 10.8 μM, 9.4 μM and 11.5 μM respectively, and that 8e was effective against HL-60 with an IC 50 at 4.6 μM. Compounds 8f–h showed a significant inhibitory effect on HUVEC growth and migration in vitro , among which 8h inhibited HUVEC growth with an IC 50 at 6.4 μM and HUVEC migration by 67.6% and 89.7% at 2.5 μg mL −1 and 10 μg mL −1 respectively. More spectacularly, docking study indicated that compound 8h might target the ATP binding site of VEGFR2. In addition, compounds 8a , 8f–h exhibited moderate in vivo antitumor efficacy against the S180 xenograft in ICR mice by 22.4–29.6% tumor weight inhibition.