Abstract |
Cultured rat astrocytes and C6 rat glioma were used as a differential screen for a variety of 1,2,3,4-tetrahydroisoquinoline (THI) derivatives. Compound 1 [1-( biphenyl-4-ylmethyl)-1,2,3,4- tetrahydroisoquinoline-6,7-diol hydrochloride] selectively blocked the growth of C6 glioma leaving normal astrocytes relatively unaffected. The potential for clinical utility of 1 was further substantiated in human gliomas and other tumor cell lines. Preliminary SAR of this activity was characterized by synthesis and testing of several THI and conformationally flexible variants.
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Authors | Michael L Mohler, Gyong-Suk Kang, Seoung-Soo Hong, Renukadevi Patil, Oleg V Kirichenko, Wei Li, Igor M Rakov, Eldon E Geisert, Duane D Miller |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 49
Issue 19
Pg. 5845-8
(Sep 21 2006)
ISSN: 0022-2623 [Print] United States |
PMID | 16970409
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol
- Antineoplastic Agents
- Biphenyl Compounds
- Isoquinolines
- Tetrahydroisoquinolines
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Topics |
- Animals
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Astrocytes
(drug effects)
- Biphenyl Compounds
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Cells, Cultured
- Drug Screening Assays, Antitumor
- Glioma
- Humans
- Isoquinolines
(chemical synthesis, chemistry, pharmacology)
- Molecular Conformation
- Rats
- Structure-Activity Relationship
- Tetrahydroisoquinolines
(chemical synthesis, chemistry, pharmacology)
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