title: Design and synthesis of the first generation of dithiolane thiazolidinedione- and phenylacetic acid-based PPARgamma agonists.
abstract: A series of novel derivatives of potent antioxidant vitamin, alpha-lipoic acid, and related analogues were designed, synthesized, and evaluated for their PPARgamma agonist activities. Compounds 9a and the water soluble analogue11e were found to be potent PPARgamma agonists. Compound 9a appeared to have a significant role in improving insulin sensitivity and reducing triglyceride levels in fa/fa rats as well as inhibited proliferation of a variety of normal and neoplastic cultured human cell types. These novel compounds may prove efficacious not only in the treatment of Type 2 diabetes, but also atherosclerosis, prevention of vascular restenosis, and inflammatory skin diseases.
authors.affiliation: Laboratory for Applied Drug Design and Synthesis, Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, 38677, USA.
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.forename: Meenakshi S
authors.initials: MS
authors.lastname: Venkatraman
authors.forename: Cassia S
authors.initials: CS
authors.lastname: Mizuno
authors.forename: Prashant V
authors.initials: PV
authors.lastname: Desai
authors.forename: Akshay
authors.initials: A
authors.lastname: Patny
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Benson
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Ho
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Harrihar A
authors.initials: HA
authors.lastname: Pershadsingh
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Avery
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007333:Insulin Resistance; D007378:Interleukins / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000960:Hypolipidemic Agents; D007378:Interleukins; C513152:N-(2-(4-((2,4-dioxo-1,3-thiazolidin-5-yl)methyl)phenoxy)ethyl)-5-(1,2-dithiolan-3-yl)-N-methylpentanamide; D047495:PPAR gamma; D010648:Phenylacetates; D045162:Thiazolidinediones; D008063:Thioctic Acid