title: Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy.
abstract: Androgens' metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17β-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects.
authors.affiliation: Department of Pharmaceutical Sciences, University of Calabria, Rende (CS), Italy.
authors.forename: F
authors.initials: F
authors.lastname: Aiello
authors.forename: A
authors.initials: A
authors.lastname: Garofalo
authors.forename: A M
authors.initials: AM
authors.lastname: Aloisi
authors.forename: S
authors.initials: S
authors.lastname: Lamponi
authors.forename: A
authors.initials: A
authors.lastname: Magnani
authors.forename: A
authors.initials: A
authors.lastname: Petroni
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D045165:Testosterone Congeners / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004952:Esters; D005231:Fatty Acids, Unsaturated; D045165:Testosterone Congeners