The inhibition of SOS-responses and MDR by phenothiazine-metal complexes.
The gene of multidrug resistance (mdr) is inducible by different environmental stresses (SOS gene). We tested the inhibitory action of some new metal complexes of phenothiazines on megacin encoding bacterial gene induced by mitomycin-C as an example of "SOS induction" and on efflux pump of mouse lymphoma cells. The interaction of compounds to DNA was measured by thermal stability of DNA. It was found that metal co-ordination complexes of trifluoperazine (TFP) and chlorpromazine (CPZ) added before mitomycin administration have an inhibitory action on megacine induction. The TFP-V(IV) complex was effective at a lower concentration than TFP alone. The inhibitory effect of some metal coordinating complexes (TFP-Cu(II) and TFP- V(IV)) exceeded the action of TFP alone on efflux pumps. We propose that these compounds can form a complex with the regulatory protein or DNA resulting in the inhibition of SOS response and inhibit the mdr function by inactivating the P-glycoprotein as well.
Nacsa
J
J
Department of Microbiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Nagy
L
L
Sharples
D
D
Hevér
A
A
Szabó
D
D
Ocsovszki
I
I
Varga
A
A
König
S
S
Molnár
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001410:Bacillus megaterium / Q000187:drug effects / Q000378:metabolism; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D016399:Lymphoma, T-Cell / Q000378:metabolism; D008530:Megacins / Q000096:biosynthesis; D008670:Metals / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology*; D013014:SOS Response, Genetics / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004269:DNA, Bacterial; D004273:DNA, Neoplasm; D008530:Megacins; D008670:Metals; D010640:Phenothiazines; D016685:Mitomycin