title: Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists.
abstract: Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Kharbanda
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Mohammad Sarwar
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Hinna
authors.initials: H
authors.lastname: Hamid
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Kalim
authors.initials: K
authors.lastname: Javed
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Bano
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi, 110 062, India.
authors.forename: Yakub
authors.initials: Y
authors.lastname: Ali
authors.affiliation: CSIR Unit for Research and Development of Information Products, Pune, 411038, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Dhulap
authors.affiliation: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, 110025, India.
authors.forename: Perwez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, 110025, India.
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D029222:Piper nigrum / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D010880:Piperidines
keywords: PPAR-γ; amide linkage; antidiabetic; gene expression; piperine