Isolation of two cellular lines resistant to ribonucleotide reductase inhibitors to investigate the inhibitory activity of 2,2'-bipyridyl-6-carbothioamide.
The mechanism of action of a synthetic compound--2,2'-bipyridyl-6-carbothioamide--was investigated by developing tumor lines resistant to it (P388-R1.5 and P388-R4). P388-R4 is resistant to inhibitors of ribonucleotide reductase (RR) while no resistance was observed to antitumor drugs having other targets (except to bleomycin). The resistance to inhibitors of the RR M2 subunit is higher than that to compounds active on the RR M1 subunit. Moreover, murine chromosome 12, in which the M2 structural gene was recently localized, was trisomic in the resistant lines. We conclude that it is possible to consider BPYTA a new inhibitor of the RR M2 subunit.
Nocentini
G
G
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Federici
F
F
Armellini
R
R
Franchetti
P
P
Barzi
A
A
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D007621:Karyotyping; D007941:Leukemia P388 / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015082:2,2'-Dipyridyl; C033291:2,2'-bipyridyl-6-carbothioamide; D012264:Ribonucleotide Reductases