Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues.

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.

• 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)

Chemical References

• 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol
• Antineoplastic Agents
• Biphenyl Compounds
• Isoquinolines
• Tetrahydroisoquinolines

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)