Inhibition of tumor cell growth by Schiff bases of hydroxysemicarbazide.
The inhibitory activities of Schiff bases of hydroxysemicarbazide (HSC) against eight human and murine tumor cell lines and one non-cancer cell line were studied using MTS/PES microculture tetrazolium and methylene blue assays. Compounds 1 (1-[9-(10-methylanthryl)methylene]-4-HSC), 2 (1-[2-hydroxy-3,5-dibromobenzylidene]-4-HSC) and 3 (1-[2,3,4-trihydroxybenzylidene]-4-HSC), which have been shown to be active against murine leukemia L1210 cells in our laboratories, inhibited human leukemia CCRF-CEM cells with similar IC50s ranging from 2.7 to 7.0 microM. Of the compounds tested against attached tumor cell lines (B16, CHO, HT29, ZR75) at 50 microM concentration, compound 1 showed the strongest inhibition, followed by 4 (1-[2-(5-nitrothienyl)methylene]-4-HSC), 2 and 5 (1-[2-hydroxy-3,5-diiodobenzylidene]-4-HSC) with more than 50% inhibition. The IC50s of compound 1 were found to range from 2.7 to 12 microM against the attached tumor cell lines examined. As compared with hydroxyurea, compound 1 had more favorable selectivity against tumor cells. Further more, compound 1 was found to have IC50s of 2.8 and 6.5 microM against hydroxyurea-resistant and gemcitabine-resistant KB cells, respectively, but had no cross-resistance with hydroxyurea and gemcitabine (two known ribonucleotide reductase inhibitors acting at different sites of the same enzyme). In conclusion, several Schiff bases of HSC showed inhibition of tumor cell growth at micromolar concentration and had no cross-resistance with hydroxyurea-resistant KB cells.
Ren
S
S
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90089-9121, USA.
Tokes
Z A
ZA
Csipke
C
C
Zhou
B
B
Yen
Y
Y
Lien
E J
EJ
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D012545:Schiff Bases / Q000494:pharmacology*; D012663:Semicarbazides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D012545:Schiff Bases; D012663:Semicarbazides