TY - JOUR
T1 - Synthesis and cytotoxicity evaluation of some 8-hydroxyquinoline derivatives
AU - Shen, Ai Yu
AU - Wu, Sheng Nan
AU - Chiu, Chih Tsao
PY - 1999/5/1
Y1 - 1999/5/1
N2 - 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.
AB - 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.
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U2 - 10.1211/0022357991772826
DO - 10.1211/0022357991772826
M3 - Article
C2 - 10411213
AN - SCOPUS:0033032774
VL - 51
SP - 543
EP - 548
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 5
ER -