Synthesis, structure and cytotoxicity of organoammonium Synthesis, structure and cytotoxicity of organoammonium selenites selenites ² Edmunds Lukevics*, Pavel Arsenyan, Irina Shestakova, Ilona Domracheva, Iveta Kanepe, Sergey Belyakov, Juris Popelis and Olga Pudova Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia Received 11 May 2001; Accepted 7 December 2001 New selenites of different organic bases have been prepared by the reaction of selenium dioxide with aliphatic and heterocyclic amines in an aqueous medium. Their structure was confirmed by 1 H, 13 C and 77 Se NMR data and, in the case of triethanolammonium hydroselenite [HN  CH 2 CH 2 OH) 3 HSeO 3 ], by X-ray analysis. Most of these selenites have an expressed cytotoxic activity on the MG-22A mouse hepatoma), HT-1080 human fibrosarcoma), B16 mouse melanoma), and Neuro 2A mouse neuroblastoma) cell lines. The substances studied were also active in vivo against sarcoma S-180. Copyright # 2002 John Wiley & Sons, Ltd. KEYWORDS: antitumor activity; cytotoxicity; morphology; selenium; X-ray INTRODUCTION Selenium ranks 70th in abundance among the elements and constitutes approximately 10 5 % of the Earth's crust. 1 In biology it was long considered as a dangerous poison, until it was identified as an essential trace element for animals. The fundamental importance of selenium for biology has become increasingly clear as new research has shown an unsus- pected role of this element for human health. 2,3 As selenocysteine, selenium is a component of selenoproteins, some of which have important enzymic functions, in this context being best known as an antioxidant and catalyst in the reduction of hydrogen peroxide; and the family of selenium-dependent glutathione peroxidases is involved on the processing of lipid or phospholipid hydroperoxides to harmless products. 4 Selenium has additional important effects, particularly in relation to the immune function. 5 Selenium deficiency is also linked to the progress of some viral infections. 6 Administration of trace quantities of Na 2 SeO 3 or Na 2 SeO 4 can successfully treat Keshan disease. 7 Organic and inorganic selenium derivatives are effective in inhibition of a wide range of tumors. There is evidence that selenium protects against certain human cancers. 3,8±11 In order to investigate the relationship between serum sele- nium content and the risk of cancer, some thousands of serum samples were obtained from cancerous and non- cancerous patients. In this cohort, the incidence of cancer in the non-cancerous patients was followed for the subsequent 3 years. The serum selenium level of non-cancerous patients who later developed cancer during the 3 years was determined and compared with that of the non-cancerous patients. A higher incidence of cancer was observed in the lower serum selenium patients of the non-cancerous group. The serum selenium level in cancerous patients was significantly lower than in non-cancerous patients. These results suggest that the low serum selenium level in cancerous patients may not be induced by the tumor, but it was more likely already present before the tumor. The ratio between the non-cancerous and cancerous groups was estimated to be 1.95:1, suggesting a higher risk of cancer in the low serum selenium group. 10 Taking into account the importance of the selenium element in the organism, pyridinium, quinolinium, bipy- ridinium, phenanthrolinium, imidazolinium, benzimidazo- linium and ethanolammonium selenites were synthesized to study the influence of cation structure on cytotoxic effect. Their antitumor activity on HT-1080, MG-22A, B-16 and Neuro 2A cell lines and in vivo S-180) was investigated. MATERIALS AND METHODS Crystal data determination The crystals of compound 13 are monoclinic, space group *Correspondence to: E. Lukevics, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia. E-mail: pavel.arsenyan@lycos.com ² This paper is based on work presented at the 5th International Conference on Environmental and Biological Aspects of Main-Group Organometals ICEBAMO-5) held at Schielleiten, near Graz, Austria, 5±9 June 2001. DOI:10.1002/aoc.276 Copyright # 2002 John Wiley & Sons, Ltd. APPLIED ORGANOMETALLIC CHEMISTRY Appl. Organometal. Chem. 2002; 16: 228±234