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 μM. Of the compounds tested against attached tumor cell lines (B16, CHO, HT29, ZR75) at 50 μM 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 μM 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 μM 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.