title: Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.
abstract: A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Nazreen
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: msalam5555@gmail.com.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Mohammad Shahar
authors.initials: MS
authors.lastname: Yar
authors.affiliation: CSIR Unit for Research and Development of Information Products, Pune 411 038, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Dhulap
authors.affiliation: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India.
authors.forename: Perwez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, New Delhi, India.
authors.forename: M A Q
authors.initials: MA
authors.lastname: Pasha
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Bano
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Mohammad Mahboob
authors.initials: MM
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Saqlain
authors.initials: S
authors.lastname: Haider
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Kharbanda
authors.affiliation: Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: Yakub
authors.initials: Y
authors.lastname: Ali
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors.forename: K K
authors.initials: KK
authors.lastname: Pillai
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment; D013311:Streptozocin; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D013311:Streptozocin
keywords: 2,4-Thiazolidinedione; Antidiabetic activity; Chromone; Hepatotoxicity; PPAR-γ