Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines

Jianyu Lu, Izumi Maezawa, Sahani Weerasekara, Ramazan Erenler, Tuyen D T Nguyen, James Nguyen, Luxi Z. Swisher, Jun Li, Lee-Way Jin, Alok Ranjan, Sanjay K. Srivastava, Duy H. Hua

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

A new series of fifteen 5-, 6-, and 8-appended 4-methylquinolines were synthesized and evaluated for their neural protective activities. Selected compounds were further examined for their inhibition of glycogen synthase kinase-3β (GSK-3β) and protein kinase C (PKC). Two most potent analogs, compounds 3 and 10, show nanomolar protective activities in amyloid β-induced MC65 cells and enzymatic inhibitory activities against GSK-3β, but poor PKC inhibitory activities. Using normal mouse model, the distribution of the most potent analog 3 in various tissues and possible toxic effects in the locomotors and inhibition of liver transaminases activities were carried out. No apparent decline of locomotor activity and no inhibition of liver transaminases were found. The compound appears to be safe for long-term use in Alzheimer's disease mouse model.

Original languageEnglish (US)
Pages (from-to)3392-3397
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number15
DOIs
StatePublished - Aug 1 2014

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Glycogen synthase kinase-3β
  • Neural protective activity
  • Protein kinase C
  • Quinolines

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

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  • Cite this

    Lu, J., Maezawa, I., Weerasekara, S., Erenler, R., Nguyen, T. D. T., Nguyen, J., Swisher, L. Z., Li, J., Jin, L-W., Ranjan, A., Srivastava, S. K., & Hua, D. H. (2014). Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines. Bioorganic and Medicinal Chemistry Letters, 24(15), 3392-3397. https://doi.org/10.1016/j.bmcl.2014.05.085