Biological potency of organic selenium compounds IV. Straight-chain dialkylmono- and diselenides

Abstract

A series of symmetrical, straight chain dialkyl selenides, ▪, with alkyl chains of 2 to 11 carbon atoms was tested for activity in the prevention of dietary necrotic liver degeneration. Though not very active, these alkanes showed the same regularities in the interrelationship between potency and length of the carbon chain as seleno-dicarboxylic acids, ▪, and selena-carboxylic acids, ▪. Activity of compounds with short alkyl chains, C 2 to C 4, was low, the pentyl derivative was five times more potent, from C 5 to C 11 an alternating effect was apparent, and chain lengths C 9 to C 11 showed optimal activity. Principally the same regularities were seen with a series of dialkyl diselenides, ▪, comprising members with alkyl chains of 3 to 21 carbon atoms, but the diselenides were much more potent than the monoselenides. The alternating effect appeared from C 2 to C 12, with the exception of the C 7 position. The dinonyl and diundecyl diselenides were comparable in potency to α-Factor 3. They are among the most potent selenium compounds found. Beyond chain length C 12 activity was low and no obvious trends were detected. Even the highest member of the series, constituting a diselena-paraffin with 44 atoms in one chain, showed some activity. The pattern for the structure-activity interrelationship of dialkyl diselenides is distinctly different from that of the corresponding diseleno-dicarboxylic acids. It has previously been seen only in monoseleno compounds and may indicate similar or identical pathways of utilization. The lipid/water distribution coefficient does not significantly affect potency against dietary liver necrosis.