Synthesis and cytotoxicity evaluation of some 8-hydroxyquinoline derivatives

Ai Yu Shen, Sheng Nan Wu, Chih Tsao Chiu

研究成果: Article同行評審

56 引文 斯高帕斯(Scopus)

摘要

Interest in Mannich bases of 8-hydroxyquinoline stems from reports of their high potency against human cancer cells. In the search for potential anticancer drug candidates, Mannich bases of 8-hydroxyquinoline (7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline, 7-piperidinomethyl-8-hydroxyquinoline and 7-diethylaminomethyl-8-hydroxyquinoline) were synthesised by reaction with various secondary amines and formaldehyde. They were prepared as hydrochlorides. The cytotoxic activity of 7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline and 7-diethylaminomethyl-8-hydroxyquinoline compounds in the National Cancer Institute in-vitro cancer cell line panel was determined. It was found that they exhibited substantial cytotoxic activity against leukaemia. The log concentration of 7-pyrrolidinomethyl-8-hydroxyquinoline, 7-morpholinomethyl-8-hydroxyquinoline and 7-diethylaminomethyl-8-hydroxyquinoline that inhibited 50% of 60 cell lines' growth were -4.81M, -5.09M and -5.35M, respectively. Compound 7-pyrrolidinomethyl-8-hydroxyquinoline was selected for further in-vivo testing. The electrophysiological effect of 7-pyrrolidinomethyl-8-hydroxyquinoline also was tested in human myeloma cells (RPMI 8226). The outward current was voltage dependent, activating at -40 mV and believed to be the voltage-activated K+ current I(K(V)) 7-Pyrrolidinomethyl-8-hydroxyquinoloine (1-30 μM) caused the inhibition of I(K(V)) in a concentration-dependent manner. The IC50 value of 7-pyrrolidinomethyl-8-hydroxyquinoline-induced inhibition of I(K(V)) is 23 μM. The GI50 value of 7-pyrrolidinomethyl-8-hydroxyquinoline-induced inhibition of cell growth is 14 μM. The results suggest that at least part of the cytotoxicity effect of 7-pyrrolidinomethyl-8-hydroxyquinoline on myeloma cells could be related to blockade of voltage-activated K+ channels.

原文English
頁(從 - 到)543-548
頁數6
期刊Journal of Pharmacy and Pharmacology
51
發行號5
DOIs
出版狀態Published - 1999 五月 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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