title: Novel benzenesulfonylureas containing thiophenylpyrazoline moiety as potential antidiabetic and anticancer agents.
abstract: In the present study a library of twenty six benzenesulfonylureas containing thiophenylpyrazoline moiety has been synthesized. All the compounds were docked against PPAR-γ target. Most of the compounds displayed higher dock score than standard drugs, glibenclamide and rosiglitazone. All the synthesized compounds were primarily evaluated for their antidiabetic effect by oral glucose tolerance test. Further assessment of antidiabetic potential of sixteen active compounds was then done on STZ induced diabetic model. The results of in vivo activity by both the methods were found to be consistent with each other as well as with docking studies. Change in body weight of STZ induced animals post treatment was also assessed at the end of study. In vitro PPAR-γ transactivation assay was performed on active compounds in order to validate docking results and the most active compound 3 k was also shown to elevate gene expression of PPAR-γ. Furthermore, the compounds were screened by National Cancer Institute, Bethesda for anticancer effect and two compounds 3h and 3 i were selected at one dose level since they exhibited sensitivity towards tumor cell lines (mainly melanoma).
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. Electronic address: msalam@jamiahamdard.ac.in.
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: Syed
authors.initials: S
authors.lastname: Shafi
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: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, India.
authors.forename: Perwez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology, Delhi, India.
authors.forename: M A Q
authors.initials: MA
authors.lastname: Pasha
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: 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: Syed
authors.initials: S
authors.lastname: Nazreen
authors.affiliation: Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110 062, India.
authors.forename: Saqlain
authors.initials: S
authors.lastname: Haider
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D062105:Molecular Docking Simulation; D047495:PPAR gamma / Q000737:chemistry / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011720:Pyrazoles; D013453:Sulfonylurea Compounds
keywords: 2-Acetylthiophene; Anticancer; Antidiabetic; Gene expression; PPAR-γ; Sulfonylureas