-transparent.png){kind=logo}
The effects of eight isoquinolinesulphonamide compounds on resistance to vinblastine in adriamycin-resistant mouse leukaemia cells (P388/ADR) which overexpress the relative molecular weight (M(r)) 140 kDa P-glycoprotein in the plasma membrane were investigated. N-[2-(Methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) and N-(2-aminoethyl)-5-isoquinolinesulphonamide (H-9) did not reverse vinblastine resistance. N-[2-[N-[3-(4-Chlorophenyl)-2-propenyl]amino] ethyl]-5-isoquinolinesulphonamide (H-86) and N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl] amino]ethyl]-5-isoquinolinesulphonamide (H-87) caused accumulation of intracellular vinblastine and inhibition of vinblastine efflux from the cells and reversed the resistance. Addition of an aminoethyl group to the nitrogen atom of the sulphonamide group (W-66) or a formyl group at the terminal amino group (H-85) of H-86 reduced those activities. Conversion of the chlorophenyl group of H-87 to pyridinyl (H-31) or furanyl (H-34) markedly decreased activities against the drug resistance. The activity against vinblastine accumulation closely correlated with the apparent partition coefficient of compounds. These compounds dose-dependently inhibited photoaffinity labelling of a photosensitive analogue of vinblastine, N-(p-azido-(3-[125I)salicyl)-N'-beta-aminoethyl-vindesine ([125I]NASV), and there was a good correlation between inhibition of [125I]NASV-photolabelling and hydrophobicity. Although these isoquinolinesulphonamides inhibited protein kinase A with different magnitudes, this activity did not correlate with the effect on the drug resistance. These results indicate that isoquinolinesulphonamide compounds with a hydrophobic group interact with antitumour drugs on P-glycoprotein and reverse multidrug resistance without involvement of their activity on protein kinase A.
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
September 1990,
British journal of cancer,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
July 1988,
Cytometry,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
July 2001,
The Journal of pharmacy and pharmacology,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
April 1993,
Cancer research,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
April 1987,
Japanese journal of cancer research : Gann,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
February 1994,
International journal of oncology,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
September 2002,
Toxicology letters,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
November 2009,
Cancer research,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
January 1997,
Oncology reports,
S Nakamura, and
S Wakusawa, and
K Tajima, and
K Miyamoto, and
M Hagiwara, and
H Hidaka
December 1993,
Molecular and cellular biology,
