The Synthesis and Antineoplastic Properties of Selenoguanine, Selenocytosine and Related Compounds¹

Abstract

A mixture of 4 g. (0.032 mole) of II and 2.65 g. (0.035 mole) of chloroacetonitrile in 20 ml. of benzene was refluxed for 90 min. The separated hydrochloride was collected, the base liberated with 10% sodium hydroxide, extracted with ether and distilled.3-/3-Aminoethyl-8-methyl-3,8-diazabicyclo [3.2.1] octane (XXIV) .-To a stirred suspension of 2.3 g. (0.06 mole) of lithium aluminum hydride in 150 ml. of dry tetrahydrofuran at 0°, 3.2 g. (0.0197 mole) of XXIII diluted with 10 ml. of tetrahydrofuran was added. The reaction mixture was refluxed for 3 hr., cooled to -5°and cautiously decomposed with 8 ml. of water. After stirring for 1 hr. at room temperature, the inorganic material was filtered and thoroughly washed with tetrahydrofuran. Tin; filtrate was dried over sodium sulfate, the solvent evaporated and the residue distilled.3-Guanidinoethyl-8-methyl-3,8-diazabicyclo[3.2.1] octane (XXV) .-A stirred mixture of 2.2 g. (0.013 mole) of XXIV, 4.8 g.(0.020 mole) of S-ethylisothiuronium bromide and 30 ml. of chloroform was refluxed for 5 hr., under an efficient hood. A viscous oil separated and solidified on cooling. The chloroform solution was decanted and stored. The solid crop (4 g.) after washing with ether was crystallized twice from isopropyl alcohol (200 ml.)to give 1.7 g. (35%) of the dihydrobromide of XXV, m.p. 230-233°. The chloroform solution was evaporated and the oily residue was crystallized from isopropyl alcohol to give 1.7 g. (45%) of XXV monohydrobromide. 8-Methyl-3-nitroso-3,8-diazabicyclo [3.2.1] octane (XXVI).-To a stirred solution at 0°of 7.3 g. (0.058 mole) of II in 29 ml. of 2 N hydrochloric acid, was added dropwise a solution of 4.5 g. (0.065 mole) of sodium nitrite in 10 ml. of water. The reaction mixture was kept, at room temperature for 2 hr., cooled, made alkaline with 50%. sodium hydroxide solution and extracted with ether. The extract was dried over sodium sulfate, the solvent evaporated and the residue distilled.

Genotoxicity of two pharmacologically important selenium compounds (selenocystine and selenopuridine) in cultured human blood lymphocytes

“…In conclusion, the findings observed in the present study may explain, at least in part, inhibitory effects of organoselenium against the growth of viruses (Kirsi et al, 1983), bacteria (Mautner et al, 1958), fungi (Kunert, 1989) and some experimental cancer models (Mautner et al, 1963;Chu and Davidson, 1972;Ross et al, 1973;Poirier and Milner, 1979;Greed and Milner, 1980;Milner and Hsu, 1981;Srivastava and Robins, 1983). Finally, it should be kept in mind that further studies using these and other forms of selenium are required before drawing conclusive conclusions in this area.…”

“…These analogs have been found to be not only less toxic, but also more potent against viruses (Kirsi et al, 1983) and tumors (Mautner et al, 1963;Chu and Davidson, 1972;Ross et al, 1973;Srivastava and Robins, 1983).…”

Derivatization of DNAs with selenium at 6-position of guanine for function and crystal structure studies

“…Despite the synthesis of the 2′-deoxy-6-selenoguanosine and its derivatives several decades ago (21,22), synthesis of nucleic acids containing the Se-guanine remained a challenge, even though 6-S-purines have been introduced into nucleic acids (23,24). To explore the Se derivatization of guanine for structure and function studies, we report here the synthesis of a 6-Se-2′-deoxyguanosine phosphoramidite, its incorporation into oligonucleotides, and Se-DNA duplex stability investigation via UV-melting study.…”

Tautomers and Acid Dissociation Constants of 6-Selenoguanine from Density Functional Theoretical Calculations

“…6-Selenoguanine (SeG) has a significant activity against L5178Y lymphoma cells. 1 However, the detailed mechanism of the antiplastic action is not known yet. Information on the acid dissociation constants and the tautomerism of the molecules is required to provide a molecular level understanding of biological processes.…”