Synthesis and biological assessment of long-acting estradiol fatty acid esters in ovariectomized rats.
Diesters of 17 beta-estradiol using palmitic acid (16:0) and oleic acid (18:1, cis-9-Octadecenoic acid) have been synthesized for potential evaluation as long-acting compounds. Female castrated rats were injected 1 mumol of estradiol dipalmitate and estradiol dioleate, using estradiol benzoate and estradiol enanthate as controls. Biological activity was determined by uterine wet weight and uterine diameter as well as on the suppression of serum anterior pituitary gonadotropins. A delayed absorption of estradiol was observed after administration of both diesters which was well correlated with the duration of biological effects. The data demonstrate that esterification with palmitic or oleic acids at 3 and 17 positions provides long-acting properties to 17 beta-estradiol, which could be applied in substitutive therapy and or in hormonal contraception.
D000818:Animals; D003692:Delayed-Action Preparations; D004958:Estradiol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010052:Ovariectomy; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D003692:Delayed-Action Preparations; D005227:Fatty Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D019301:Oleic Acid; D019308:Palmitic Acid; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone