The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings.
Two recently synthesized groups of acridine cytostatics containing fused heterocyclic ring(s): pyrazoloacridines (PAC) and pyrazolopyrimidoacridines (PPAC) were tested in regard to their in vitro cytotoxic activity towards a panel of sensitive and resistant human tumor cell lines. The obtained results corroborate our earlier hypothesis on the essential role of heterocyclic ring fused to the acridine moiety in the ability of acridine cytostatics to overcome multidrug resistance of tumor cells. The presence, location and kind of substituents considerably influenced both the cytotoxic activity of the derivatives and their ability to overcome multidrug resistance. The same factors also affected the cytostatics ability to differentiate between tumor cell lines with various types of drug exporting pumps.
Department of Pharmaceutical Technology and Biochemistry, Chemical Faculty, Technical University of Gdańsk, Poland. majka@altis.chem.pg.gda.pl
Maria M
MM
Bontemps-Gracz
Agnieszka
A
Kupiec
Ippolito
I
Antonini
Edward
E
Borowski
D000166:Acridines / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D006801:Humans; D066298:In Vitro Techniques; D011720:Pyrazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000166:Acridines; D011720:Pyrazoles; C064541:NSC 366140