title: Antidiabetic effect of novel benzenesulfonylureas as PPAR-γ agonists and their anticancer effect.
abstract: Twenty one pyrazoline containing benzenesulfonylureas were synthesized and docked against PPAR-γ target. All the compounds were first screened for their antidiabetic potential by oral glucose tolerance test and then six active compounds were assessed on STZ diabetic model. It was found that five compounds showed significantly high antidiabetic activity in comparison to glibenclamide as well as rosiglitazone (standard drugs). The active compounds were evaluated for their effect on body weight since weight management is one of the main concerns associated with sulfonylureas. Finally, the most active compound 6f was shown to elevate PPAR-γ gene expression. The synthesized compounds were also screened for anticancer activity by National Cancer Institute. Five compounds (5i, 6e, 6g, 6i and 6j) were selected at one dose level and showed potency against cancers.
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: 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: Yakub
authors.initials: Y
authors.lastname: Ali
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D011720:Pyrazoles; D013453:Sulfonylurea Compounds; D013311:Streptozocin
keywords: Anticancer; Antidiabetic; Gene expression; PPAR-γ; Sulfonylureas