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

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 exe...

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Autores principales: Ezell, Scharri J., Li, Haibo, Xu, Hongxia, Zhang, Xiangrong, Gurpinar, Evrim, Zhang, Xu, Rayburn, Elizabeth R., Sommers, Charnell I., Yang, Xinyi, Velu, Sadanandan E., Wang, Wei, Zhang, Ruiwen
Formato: Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920546/
https://www.ncbi.nlm.nih.gov/pubmed/20714427
http://dx.doi.org/10.3390/md8072129
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author Ezell, Scharri J.
Li, Haibo
Xu, Hongxia
Zhang, Xiangrong
Gurpinar, Evrim
Zhang, Xu
Rayburn, Elizabeth R.
Sommers, Charnell I.
Yang, Xinyi
Velu, Sadanandan E.
Wang, Wei
Zhang, Ruiwen
author_facet Ezell, Scharri J.
Li, Haibo
Xu, Hongxia
Zhang, Xiangrong
Gurpinar, Evrim
Zhang, Xu
Rayburn, Elizabeth R.
Sommers, Charnell I.
Yang, Xinyi
Velu, Sadanandan E.
Wang, Wei
Zhang, Ruiwen
author_sort Ezell, Scharri J.
collection PubMed
description 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.
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spelling pubmed-29205462010-08-16 Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent Ezell, Scharri J. Li, Haibo Xu, Hongxia Zhang, Xiangrong Gurpinar, Evrim Zhang, Xu Rayburn, Elizabeth R. Sommers, Charnell I. Yang, Xinyi Velu, Sadanandan E. Wang, Wei Zhang, Ruiwen Mar Drugs Article 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. Molecular Diversity Preservation International 2010-07-13 /pmc/articles/PMC2920546/ /pubmed/20714427 http://dx.doi.org/10.3390/md8072129 Text en © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Ezell, Scharri J.
Li, Haibo
Xu, Hongxia
Zhang, Xiangrong
Gurpinar, Evrim
Zhang, Xu
Rayburn, Elizabeth R.
Sommers, Charnell I.
Yang, Xinyi
Velu, Sadanandan E.
Wang, Wei
Zhang, Ruiwen
Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title_full Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title_fullStr Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title_full_unstemmed Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title_short Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent
title_sort preclinical pharmacology of ba-tpq, a novel synthetic iminoquinone anticancer agent
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920546/
https://www.ncbi.nlm.nih.gov/pubmed/20714427
http://dx.doi.org/10.3390/md8072129
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