Influence of lipophilicity on cytotoxicity of anthracyclines in LoVo and LoVo/Dx human cell lines.
Quantitative structure-activity relationship studies aimed at improving drug activity profiles require the determination of the physicochemical properties possibly involved in biological action. The lipophilic character of selected anthracyclines has been measured by means of reverse-phase high performance liquid chromatography, selecting appropriate experimental conditions. The capacity coefficients at zero percentage of the organic phase (log K0), which are retention indexes, have been used as lipophilicity descriptors in a QSAR study, involving as biological data the cytotoxicity of anthracyclines in a doxorubicin-sensitive (LoVo) and in a doxorubicin-resistant (LoVo/Dx) human cell lines. The results obtained in these in vitro models indicate that lipophilicity plays a role in anthracycline activity, influencing drug availability at the site of action.
Facchetti
I
I
Farmitalia-Carlo Erba srl, Erbamont Group, Milan, Italy.
Grandi
M
M
Cucchi
P
P
Geroni
C
C
Penco
S
S
Vigevani
A
A
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D012995:Solubility; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin