title: Study on gluco-regulatory potential of glimepiride sulfonamide using in silico, in vitro and in vivo approaches.
abstract: Glimepiride sulfonamide (GS) is a drug intermediate to synthesize glimepiride (antidiabetic drug). We hypothesized that GS exerts gluco-regulatory effect because GS is comprised of the structural components of dipeptidyl peptidase-IV (DPP-IV) inhibitors sitagliptin and DPP-728and glimepiride (sulfonylurea based antidiabetic drug).We analyzed the drug-likeness and docking efficiency of GS with DPP-IV using in silico tools. Also DPP-IV inhibition assays were conducted in vitro. Gluco-regulatory potential and parameters of drug safety were evaluated on normal euglycemic and streptozotocin (STZ) induced diabetic rats. We observed strong drug-likeness and DPP-IV binding efficiency of GS. Similarly, profound DPP-IV inhibition was also observed in vitro. Studies on euglycemic and STZ induced diabetic rats revealed antidiabetic potential for GS without significant change in the studied toxicological parameters. Glimepiride sulfonamide has antidiabetic potential mainly through DPP-IV inhibition, but also through insulin stimulation and alpha-amylase inhibition.
authors.forename: Hamendra Singh
authors.initials: HS
authors.lastname: Parmar
authors.forename: Mahesh Kumar
authors.initials: MK
authors.lastname: Bhinchar
authors.forename: Muskan
authors.initials: M
authors.lastname: Bhatia
authors.forename: Nikita
authors.initials: N
authors.lastname: Chordia
authors.forename: Ishan
authors.initials: I
authors.lastname: Raval
authors.forename: Digvijay Singh
authors.initials: DS
authors.lastname: Chauhan
authors.forename: E
authors.initials: E
authors.lastname: Manivannan
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Jatwa
authors.affiliation: School of Biotechnology, Devi Ahilya University, Takshashila Campus, khandwa Road, Indore- 452001, M.P., India. hamendrasingh999@yahoo.co.in.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D003198:Computer Simulation; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D062105:Molecular Docking Simulation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; D013311:Streptozocin; C057619:glimepiride; D018819:Dipeptidyl Peptidase 4