Synthesis and investigation of new Hesperadin analogues antitumor effects on HeLa cells

Journal of Chemical Biology

Sedigheh Vafaei¹  Fereshteh Shamsipour¹  Saeeideh Hosseinzadeh¹  Mahmood Jeddi-Tehrani¹  Samira Farid¹  Saeed Balalaie¹  Seyed Shahriar Arab¹ 

[1] Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, P.O. Box: 19615-1177, 1936773493 Tehran, Iran

关键词: Aurora kinase;    Hesperadin;    Antitumor effects;    Analogues;   

DOI  :  10.1007/s12154-014-0111-3

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Hesperadin is one of the indolinones that was designed against the ATP-binding site of Aurora kinase. This molecule inhibits Aurora B kinase by phosphorylation of histone H3. In this study, new derivatives of Hesperadin containing an amide group in their structures were synthesized through sequential Ugi/palladium-catalyzed approach and in vitro antitumor activity of new compounds were evaluated by cell proliferation assay. The results show that compounds 6f, 6i, 6l, and 6o were dose-dependently inhibited in different concentrations, and IC50 values were between 35 and 43 nM. It seems that lipophilic substitution on the indolinone core with the ability to form additional hydrogen bond might lead to increased stability of structure and activity of new Hesperadin analogues.

【 授权许可】

Unknown