Reversal of multidrug resistance by novel cyclosporin A analogues and the cyclopeptolide SDZ 214-103 biosynthesized in vitro.
It was shown that cyclopeptolide SDZ 214-103 (10 microM) is more active in rhodamine-123 accumulation in actinomycin-D-resistant human lymphoma cells CCRF/ACTD400 than cyclosporin A (10 microM), but equipotent in the doxorubicin-resistant Friend erythroleukemia cell line F4-6/ADR. In F4-6/ADR cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed comparable cytotoxic effects of doxorubicin at various concentrations in the presence of SDZ 214-103 and cyclosporin A. For the other novel cyclosporin A analogues minor multidrug-resistance-modulating potency was demonstrated. At equipotent modulating doses of verapamil (10 microM) and cyclosporin A (10 microM) in the MTT assay regarding doxorubicin cytotoxicity, cyclosporin A was efficient in the rhodamine-123-uptake assay while verapamil was not active when identical incubation times were used.
Schwabe
K
K
Bundesinstitut für Arzneimittel und Medizinprodukte, Berlin, Federal Republic of Germany.
Steinheider
G
G
Lawen
A
A
Traber
R
R
Hildebrandt
A
A
D003524:Cyclosporins / Q000096:biosynthesis / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004352:Drug Resistance, Microbial / Q000502:physiology; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D005622:Friend murine leukemia virus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism; D020112:Rhodamine 123; D012235:Rhodamines / Q000493:pharmacokinetics; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D012235:Rhodamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C070510:SDZ 214-103; D003609:Dactinomycin; D020112:Rhodamine 123; D004317:Doxorubicin; C022616:thiazolyl blue