Organoammonium hydroselenites: antitumor action through radical balance regulation.
Organoammonium hydroselenites were synthesized and investigated as potential selective, anticancer prodrugs. These compounds were studied in vitro on human fibrosarcoma (HT-1080), hamster kidney endothelial (BHK 21) and normal mouse embryonic fibroblasts (NIH 3T3). Most of them were very active against HT-1080 (0.6-5.3 g/ml). Amino acid hydroselenites readily increased the nitric oxide (NO) concentration in the culture medium of HT-1080 cells (up to TG(100)=1500%); however, 4-amidohydroximinomethylpyridinium hydroselenite (TG(100)=24%) and o-phenanthrolinium hydroselenite (TG(100)=50%) were free radical inhibitors. All compounds were glutathione peroxidase inhibitors; some of them could also prevent hydrogen peroxide degradation by inhibition of catalase. The influence of the investigated ammonium hydroselenites on tumor cell (HT-1080) morphology was examined. The substances studied were also active in vivo against sarcoma S-180. The role of organoammonium hydroselenites as free radical regulators and their therapeutic antitumor are discussed.
Arsenyan
Pavel
P
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia. pavel.arsenyan@lycos.com
Shestakova
Irina
I
Rubina
Kira
K
Domracheva
Ilona
I
Nesterova
Alena
A
Vosele
Kristina
K
Pudova
Olga
O
Lukevics
Edmunds
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005609:Free Radicals; D016566:Organoselenium Compounds; D000644:Quaternary Ammonium Compounds; D002374:Catalase; D005979:Glutathione Peroxidase