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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2010-07-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/8/7/2129/ |
| _version_ | 1828112620697157632 |
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| author | Ruiwen Zhang Wei Wang Sadanandan E. Velu Xinyi Yang Charnell I. Sommers Elizabeth R. Rayburn Xu Zhang Evrim Gurpinar Hongxia Xu Xiangrong Zhang Scharri J. Ezell Haibo Li |
| author_facet | Ruiwen Zhang Wei Wang Sadanandan E. Velu Xinyi Yang Charnell I. Sommers Elizabeth R. Rayburn Xu Zhang Evrim Gurpinar Hongxia Xu Xiangrong Zhang Scharri J. Ezell Haibo Li |
| author_sort | Ruiwen Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T11:52:11Z |
| format | Article |
| id | doaj.art-93dce1ef7e914decbb5a9501a249ad62 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T11:52:11Z |
| publishDate | 2010-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-93dce1ef7e914decbb5a9501a249ad622022-12-22T04:25:17ZengMDPI AGMarine Drugs1660-33972010-07-01872129214110.3390/md8072129Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer AgentRuiwen ZhangWei WangSadanandan E. VeluXinyi YangCharnell I. SommersElizabeth R. RayburnXu ZhangEvrim GurpinarHongxia XuXiangrong ZhangScharri J. EzellHaibo LiMarine 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.http://www.mdpi.com/1660-3397/8/7/2129/marine alkaloidpharmacokineticsprotein bindingchemotherapy |
| spellingShingle | Ruiwen Zhang Wei Wang Sadanandan E. Velu Xinyi Yang Charnell I. Sommers Elizabeth R. Rayburn Xu Zhang Evrim Gurpinar Hongxia Xu Xiangrong Zhang Scharri J. Ezell Haibo Li Preclinical Pharmacology of BA-TPQ, a Novel Synthetic Iminoquinone Anticancer Agent Marine Drugs marine alkaloid pharmacokinetics protein binding chemotherapy |
| 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 | marine alkaloid pharmacokinetics protein binding chemotherapy |
| url | http://www.mdpi.com/1660-3397/8/7/2129/ |
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