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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Molecular Diversity Preservation International
2010
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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. |
format | Text |
id | pubmed-2920546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Molecular Diversity Preservation International |
record_format | MEDLINE/PubMed |
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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