title: Indole-based fibrates as potential hypolipidemic and antiobesity agents.
abstract: Hypolipidemic and antiobesity effects of the newly synthesized indole-based fibrates were evaluated in Triton WR-1339 and high fat diet (HFD)-induced hyperlipidemic rats. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton model), in which compounds 3f and 3l showed significant antidyslipidemic activity. Furthermore, these compounds 3f and 3l were found to induce significant weight loss in the visceral fat mass of HFD-fed hyperlipidemic rats without affecting the normal feeding behavior. Histological examination of the liver of rats supplemented with 3f and 3l revealed a significant decrease in steatosis when compared to the effect of the standard drug fenofibrate. Additional effects such as an increase in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catabolism of I(131)-low density lipoproteins (LDL) confirm and reinforce the efficacy of both of these compounds as a new class of dual-acting hypolipidemic and antiobesity agents.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226 001, India. sashidhar123@gmail.com
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Ravi
authors.initials: R
authors.lastname: Sonkar
authors.forename: Bhanu Shankar
authors.initials: BS
authors.lastname: Singh
authors.forename: A K
authors.initials: AK
authors.lastname: Khanna
authors.forename: Gitika
authors.initials: G
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004041:Dietary Fats; D005234:Fatty Liver / Q000517:prevention & control; D005243:Feces / Q000737:chemistry; D005247:Feeding Behavior / Q000187:drug effects; D058607:Fibric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001647:Bile Acids and Salts; D002087:Butyrates; D004041:Dietary Fats; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D007211:Indoles; D008077:Lipoproteins, LDL; D011422:Propionates; C573841:ethyl 2-(4-(bis(1-ethyl-1H-indol-3-yl)methyl)phenoxy)propanoate; C573842:ethyl 4-(4-(bis(1-methyl-1H-indol-3-yl)methyl)phenoxy)butanoate; D007862:Phosphatidylcholine-Sterol O-Acyltransferase