Synthesis and evaluation of new 1,2,3,4-tetrahydroisoquinoline analogs as antiglioma agents

Renukadevi Patil, Shivaputra Patil, Xiang Di Wang, Fei Ma, William E. Orr, Wei Li, Charles Yates, Eldon E. Geisert, Duane Miller

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Novel tetrahydroisoquinoline (THI) analogs were designed, synthesized, and their antiglioma activity was evaluated. The results showed that 6,8-dimethoxy-1-(2′-methoxybiphenyl-4-ylmethyl)-1,2,3,4- tetrahydroisoquinoline hydrochloride (25) demonstrated improved potency, and selectivity on C6 rat glioma vs cultured rat astrocytes (EC50 0.63 μM vs. 10.85 μM) compared to our recent lead molecule EDL-155 (EC 50 1.5 μM vs. 27.4 μM). The isomers of 25 were isolated using a semi-preparative high-performance liquid chromatography (HPLC) method, and their in vitro biological evaluation revealed that (+) 25 was the most active, and it was nearly 21 fold more potent than (-) 25, suggesting the antiglioma profile is influenced by stereochemical factors.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalMedicinal Chemistry Research
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2011

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Rats
Tetrahydroisoquinolines
High performance liquid chromatography
Glioma
Astrocytes
Isomers
High Pressure Liquid Chromatography
Molecules
1,2,3,4-tetrahydroisoquinoline
4-methoxybiphenyl
EDL-155
Lead
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Synthesis and evaluation of new 1,2,3,4-tetrahydroisoquinoline analogs as antiglioma agents. / Patil, Renukadevi; Patil, Shivaputra; Wang, Xiang Di; Ma, Fei; Orr, William E.; Li, Wei; Yates, Charles; Geisert, Eldon E.; Miller, Duane.

In: Medicinal Chemistry Research, Vol. 20, No. 1, 01.01.2011, p. 131-137.

Research output: Contribution to journalArticle

Patil, Renukadevi ; Patil, Shivaputra ; Wang, Xiang Di ; Ma, Fei ; Orr, William E. ; Li, Wei ; Yates, Charles ; Geisert, Eldon E. ; Miller, Duane. / Synthesis and evaluation of new 1,2,3,4-tetrahydroisoquinoline analogs as antiglioma agents. In: Medicinal Chemistry Research. 2011 ; Vol. 20, No. 1. pp. 131-137.
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