title: 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.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mohler
authors.forename: Gyong-Suk
authors.initials: GS
authors.lastname: Kang
authors.forename: Seoung-Soo
authors.initials: SS
authors.lastname: Hong
authors.forename: Renukadevi
authors.initials: R
authors.lastname: Patil
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Kirichenko
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Igor M
authors.initials: IM
authors.lastname: Rakov
authors.forename: Eldon E
authors.initials: EE
authors.lastname: Geisert
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D005910:Glioma; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C514175:1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines