Atovaquone derivatives as potent cytotoxic and apoptosis inducing agents

Jing Zhou; Lei Duan; Huaming Chen; Xiaomei Ren; Zhang Zhang; Fengtao Zhou; Jinsong Liu; Duanqing Pei; Ke Ding

doi:10.1016/j.bmcl.2009.07.044

Atovaquone derivatives as potent cytotoxic and apoptosis inducing agents

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5091-4. doi: 10.1016/j.bmcl.2009.07.044. Epub 2009 Jul 10.

Authors

Jing Zhou¹, Lei Duan, Huaming Chen, Xiaomei Ren, Zhang Zhang, Fengtao Zhou, Jinsong Liu, Duanqing Pei, Ke Ding

Affiliation

¹ Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, International Business Incubator A-3, Guangzhou Science Park, Guangzhou, China.

PMID: 19632833
DOI: 10.1016/j.bmcl.2009.07.044

Abstract

2-Piperazinyl naphthoquinones (2) and 2-piperidinyl naphthoquinones (3) were designed and synthesized as new cytotoxic and apoptosis inducing agents by utilizing the anti-parasite drug atovaquone as lead compound. Several compounds displayed significantly improved cytotoxic activities against a panel of cancer cell lines than that of atovaquone. These compounds also induced apoptosis through activating pro-apoptotic caspases 9 and 3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / toxicity
Apoptosis*
Atovaquone / analogs & derivatives*
Atovaquone / chemistry
Atovaquone / pharmacology
Caspase 3 / metabolism
Caspase 9 / metabolism
Cell Line, Tumor
Crystallography, X-Ray
Drug Design
Drug Screening Assays, Antitumor
Humans
Male
Molecular Conformation
Naphthoquinones / chemical synthesis
Naphthoquinones / chemistry*
Naphthoquinones / toxicity
Prostatic Neoplasms / drug therapy
Prostatic Neoplasms / pathology

Substances

Anti-Infective Agents
Antineoplastic Agents
Naphthoquinones
Caspase 3
Caspase 9
Atovaquone