title: Design and synthesis of pyridazinone-substituted benzenesulphonylurea derivatives as anti-hyperglycaemic agents and inhibitors of aldose reductase - an enzyme embroiled in diabetic complications.
abstract: Thirty new aryl-pyridazinone-substituted benzenesulphonylurea derivatives (I-XXX) were synthesized and evaluated for their anti-hyperglycaemic activity in glucose-fed hyperglycaemic normal rats. Twenty-three compounds (III-XI, XIV-XVII, XIX-XXIV, XXVI and XXVIII-XXX) showed more or comparable area under the curve (AUC) reduction percentage (ranging from 21.9% to 35.5%) as compared to the standard drug gliclazide (22.0%). On the basis of docking results, 18 compounds were screened for their in vitro ability to inhibit rat lens aldose reductase. Ten compounds (III-VI, XII, XVI-XVIII, XXI and XXVII) showed ARI activity with IC50 ranging from 34 to 242 μM. Out of these, two compounds IV and V showed best ARI activity which is comparable with that of quercetin. As a result, two compounds (IV and V) possessing significant dual action (anti-hyperglycaemic and aldose reductase inhibition) were identified and may be used as lead compounds for developing new drugs.
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Raed
authors.initials: R
authors.lastname: Yaseen
authors.affiliation: b Biochemistry Division, National Institute of Nutrition , Hyderabad , India .
authors.forename: H
authors.initials: H
authors.lastname: Pushpalatha
authors.affiliation: b Biochemistry Division, National Institute of Nutrition , Hyderabad , India .
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
authors.affiliation: c Department of Pharmacology , State Company for Drugs Industry and Medical Appliances , Samarra , Iraq .
authors.forename: Ameer
authors.initials: A
authors.lastname: Ismael
authors.affiliation: c Department of Pharmacology , State Company for Drugs Industry and Medical Appliances , Samarra , Iraq .
authors.forename: Ayad
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Alhamza
authors.initials: A
authors.lastname: Dheyaa
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Syed
authors.initials: S
authors.lastname: Ovais
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Pooja
authors.initials: P
authors.lastname: Rathore
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Mohammed
authors.initials: M
authors.lastname: Samim
authors.affiliation: d Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi , India , and.
authors.forename: Mymoona
authors.initials: M
authors.lastname: Akthar
authors.affiliation: d Drug Design and Medicinal Chemistry Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi , India , and.
authors.forename: Kalicharan
authors.initials: K
authors.lastname: Sharma
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Syed
authors.initials: S
authors.lastname: Shafi
authors.affiliation: e Department of Pharmacology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Surender
authors.initials: S
authors.lastname: Singh
authors.affiliation: a Department of Chemistry , Faculty of Science, Jamia Hamdard (Hamdard University) , New Delhi , India .
authors.forename: Kalim
authors.initials: K
authors.lastname: Javed
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D019540:Area Under Curve; D048909:Diabetes Complications / Q000201:enzymology*; D015195:Drug Design; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000201:enzymology*; D008297:Male; D011724:Pyridazines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis / Q000379:methods; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D011724:Pyridazines; D013453:Sulfonylurea Compounds; D000449:Aldehyde Reductase
keywords: Aldose reductase; diabetes; docking; pyridazinone; sulfonylurea