Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent

Marine Drugs

Scharri J. Ezell¹  Haibo Li¹  Hongxia Xu¹  Xiangrong Zhang¹  Evrim Gurpinar¹  Xu Zhang¹  Elizabeth R. Rayburn¹  Charnell I. Sommers¹  Xinyi Yang¹  Sadanandan E. Velu²  Wei Wang¹ 

[1] Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; E-Mails:;Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA; E-Mail:

关键词: marine alkaloid;    pharmacokinetics;    protein binding;    chemotherapy;   

DOI  :  10.3390/md8072129

来源: mdpi

【 摘 要 】

Marine natural products and their synthetic derivatives represent a major source of novel candidate anti-cancer compounds. We have recently tested the anti-cancer activity of more than forty novel compounds based on an iminoquinone makaluvamine scaffold, and have found that many of the compounds exert potent cytotoxic activity against human cancer cell lines. One of the most potent compounds, BA-TPQ [(11,12),7-(benzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one], was active against a variety of human cancer cell lines, and inhibited the growth of breast and prostate xenograft tumors in mice. However, there was some toxicity noted in the mice following administration of the compound. In order to further the development of BA-TPQ, and in a search for potential sites of accumulation that might underlie the observed toxicity of the compound, we accomplished preclinical pharmacological studies of the compound. We herein report the in vitro and in vivo pharmacological properties of BA-TPQ, including its stability in plasma, plasma protein binding, metabolism by S9 enzymes, and plasma and tissue distribution. We believe these studies will be useful for further investigations, and may be useful for other investigators examining the use of similar compounds for cancer therapy.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland