thiourea has been researched along with Leukemia-P388* in 2 studies
2 other study(ies) available for thiourea and Leukemia-P388
Article | Year |
---|---|
Replacement of an NH(3) by an iminoether in transplatin makes an antitumor drug from an inactive compound.
To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH(3) by an iminoether group, trans-[PtCl(2)(Z-HN=C(OMe)Me)(NH(3)] and trans-[PtCl(2)(E-HN=C(OMe)Me)(NH(3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC(50) values being 103, 37, and 215 microM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice. In the reaction with naked DNA, mixed Z forms monofunctional adducts that do not evolve into intrastrand cross-links but close slowly into interstrand cross-links between complementary guanine and cytosine residues. The monofunctional mixed Z adducts are removed by thiourea and glutathione. The interstrand cross-links behave as hinge joints, increasing the flexibility of DNA double helix. The mixed Z, transplatin, and cisplatin interstrand cross-links, as well as mixed Z monofunctional adducts are not specifically recognized by HMG1 protein, which was confirmed to be able to specifically recognize cisplatin d(GpG) intrastrand cross-links. These data demonstrate that the DNA interaction properties of the antitumor-active mixed Z are very similar to those of transplatin, thus suggesting that clinical inactivity of transplatin could not depend upon its peculiar DNA binding mode. Topics: Animals; Antineoplastic Agents; Cisplatin; Cross-Linking Reagents; Disease Models, Animal; DNA; DNA Adducts; DNA Footprinting; DNA Restriction Enzymes; DNA-Directed RNA Polymerases; Drug Screening Assays, Antitumor; High Mobility Group Proteins; Humans; Leukemia P388; Mice; Nucleic Acid Conformation; Oligonucleotides; Rats; Thiourea; Tumor Cells, Cultured | 2000 |
Thiourea and thiosemicarbazide derivatives structurally related to hexestrol: synthesis and anticancer and other pharmacological properties.
Two novel series of thio compounds bearing internal structural modifications of hexestrol were synthesized as potential anticancer agents. The first contains several N-substituted thiourea functions, and the second contains various N4-substituted-3-thiosemicarbazide moieties in place of one alpha-ethyl group of hexestrol dimethyl ether. The products showed no antileukemic activity in the P-388 lymphocytic leukemia system and did not exhibit any anticonvulsant or estrogenic properties. Topics: Animals; Antineoplastic Agents; Hexestrol; Leukemia P388; Mice; Semicarbazides; Structure-Activity Relationship; Thiourea | 1981 |