Design, Synthesis, and Cytotoxicity of Indolizinoquinoxaline-5,12-dione Derivatives, Novel DNA Topoisomerase IB Inhibitors

De-Qing Shen; Ning Wu; Yan-Ping Li; Zu-Ping Wu; Hong-Bin Zhang; Zhi-Shu Huang; Lian-Quan Gu; Lin-Kun An

doi:10.1071/CH09580

RESEARCH ARTICLE

Design, Synthesis, and Cytotoxicity of Indolizinoquinoxaline-5,12-dione Derivatives, Novel DNA Topoisomerase IB Inhibitors

De-Qing Shen ^A , Ning Wu ^A , Yan-Ping Li ^A , Zu-Ping Wu ^A , Hong-Bin Zhang ^B , Zhi-Shu Huang ^A , Lian-Quan Gu ^A and Lin-Kun An ^A ^C

+ Author Affiliations

- Author Affiliations

^A School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

^B Department of Medical Research, Guangzhou Liuhuaqiao Hospital, Guangzhou, 510010, China.

^C Corresponding author. Email: lssalk@mail.sysu.edu.cn

Australian Journal of Chemistry 63(7) 1116-1121 https://doi.org/10.1071/CH09580
Submitted: 5 November 2009 Accepted: 8 February 2010 Published: 15 July 2010

Abstract

A series of new indolizinoquinoxaline-5,12-dione derivatives were designed and synthesized via a heterocyclization reaction of 6,7-dichloroquinoxaline-5,8-dione with active methylene reagents and pyridine derivatives. The synthesized compounds exhibited significant activity to inhibit the growth of four human tumour cell lines, including lung adenocarcinoma cell, large-cell lung carcinoma cell, breast carcinoma cell, and ardriamycin-resistant breast carcinoma cell at micromolar range. These compounds were also investigated for their inhibition to DNA topoisomerase IB activity. The results indicated that the indolizinoquinoxaline-5,12-dione structure might be a potential pharmacophore in anti-cancer drug design.

Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 30801425), National S & T Major Project (No. 2009ZX09103–042) and Health Department of Guangdong Province (No. B2009048). We thank Professor D. Li, School of Pharmaceutical Sciences, Sun Yat-sen University, and Professor Y. M. Li, College of Pharmacy, Nankai University, for their kind help in revision of this manuscript.

References

Design, Synthesis, and Cytotoxicity of Indolizinoquinoxaline-5,12-dione Derivatives, Novel DNA Topoisomerase IB Inhibitors

Abstract

Acknowledgements

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