title: Synthesis, characterization, and preclinical evaluation of new thiazolidin-4-ones substituted with p-chlorophenoxy acetic acid and clofibric acid against insulin resistance and metabolic disorder.
abstract: We synthesized twenty thiazolidin-4-one derivatives, which were then characterized by standard chromatographic and spectroscopic methods. From the in vitro glucose uptake assay, two compounds behaved as insulin sensitizers, where they enhanced glucose uptake in isolated rat diaphragm. In high-carbohydrate diet-induced insulin resistant mice, these two thiazolidin-4-ones attenuated hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and glucose intolerance. They raised the plasma leptin but did not reverse the diabetes-induced hypoadiponectinemia. Additionally, compound 3a reduced adiposity. The test compounds were also able to reverse the disturbed liver antioxidant milieu. To conclude, these two novel thiazolidin-4-ones modulated multiple mechanisms involved in metabolic disorders, reversing insulin resistance and thus preventing the development of type-2 diabetes.
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Vasantharaju S
authors.initials: VS
authors.lastname: Gowdra
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Jayesh
authors.identifier: 0000-0001-8190-7031
authors.initials: J
authors.lastname: Mudgal
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Punit
authors.initials: P
authors.lastname: Bansal
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Pawan G
authors.initials: PG
authors.lastname: Nayak
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Seethappa A
authors.initials: SA
authors.lastname: Manohara Reddy
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Gautham G
authors.initials: GG
authors.lastname: Shenoy
authors.affiliation: Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Manna
authors.identifier: 0000-0003-3496-9920
authors.initials: M
authors.lastname: Valiathan
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Mallikarjuna R
authors.initials: MR
authors.lastname: Chamallamudi
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Gopalan K
authors.initials: GK
authors.lastname: Nampurath
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002995:Clofibric Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051381:Rats; D053778:Thiazolidines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D053778:Thiazolidines; D015084:2,4-Dichlorophenoxyacetic Acid; C007017:4-chlorophenoxyacetic acid; D002995:Clofibric Acid