Biological potency of organic selenium compounds: VI. Aliphatic seleninic acids and carboxyseleninic acids

Abstract

Straight-chain aliphatic seleninic acids, CH 3-(CH 2) n -SeOOH, with chain lengths from C 4 to C 17, a few dibasic acids of moderate chain length having seleninic acid groups on both ends of the molecule, HOOSe-(CH 2) n -SeOOH, and a series of carboxyseleninic acids, HOOC-R-SeOOH, comprising chain lengths from C 3 to C 13 and several branched chains with 5 to 7 carbon atoms were tested for potency in the prevention of dietary liver necrosis in the rat. Alkylseleninic acids showed uniformly low activities, ranging from 18% to 56% of that of selenite selenium which served as a standard. There were no discernible trends or regularities with increasing chain lengths, in contrast to other series of alkylselenium compounds. It is therefore unlikely that alkylseleninic acids are normal oxidation products of dialkyl mono- or diselenides in the organism. Compounds with seleninic acid groups at both ends of the chain were practically inactive. Carboxyseleninic acids carrying a carboxyl group distal to the seleninic acid group, on the other hand, were highly effective. A maximum of potency occurred at chain lengths C 3 and C 4, followed by a sharp decline between C 4 and C 6. A second maximum of activity occurred at C 6. There was no alternating effect. This structure/activity pattern is analogous to that of the diselenodicarboxylic acids. However, the lower carboxyseleninic acids were, per atom of selenium, twice as active as the corresponding diseleno-dicarboxylic acids, of which the higher members were less potent. It is inferred that carboxyseleninic acids may be metabolically related to diseleno-dicarboxylic acids and that C 3 and C 4 carboxyseleninic acids may play a physiological role.