Synthesis and biological evaluation of some new pyrazoline substituted benzenesulfonylurea/thiourea derivatives as anti-hyperglycaemic agents and aldose reductase inhibitors.
Seventeen new pyrazoline substituted benzenesulfonylurea/thiourea derivatives (2a-q) were synthesized and characterized by elemental analysis and various spectroscopic techniques viz; IR, (1)H NMR, (13)C NMR, and MS data. Thirteen compounds showed moderate to good anti-hyperglycaemic activity in glucose fed hyperglycaemic normal rats at the dose of 0.05 mM/kg b.w. On the basis of docking results nine compounds (2a, 2c, 2e, 2h, 2k, 2l, 2n, 2o and 2q) were evaluated for their ability to inhibit rat lens aldose reductase. Out of these six compounds (2h, 2k, 2l, 2n, 2o and 2q) were found more effective than the known ARI sorbinil. Five compounds (2h, 2k, 2l, 2n and 2o) showed significant dual action (anti-hyperglycaemic and aldose reductase inhibition).
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Syed
S
Ovais
Biochemistry Division, National Institute of Nutrition, Hyderabad, India.
H
H
Pushpalatha
Biochemistry Division, National Institute of Nutrition, Hyderabad, India.
G Bhanuprakash
GB
Reddy
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Pooja
P
Rathore
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Rafia
R
Bashir
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Shafiya
S
Yaseen
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Alhamza
A
Dheyaa
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Raed
R
Yaseen
Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.
Omprakash
O
Tanwar
Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India.
Mymoona
M
Akthar
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Mohammed
M
Samim
Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: kjaved@jamiahamdard.ac.in.
Kalim
K
Javed
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013890:Thiourea / Q000737:chemistry*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011720:Pyrazoles; D000449:Aldehyde Reductase; D013890:Thiourea
Aldose reductase inhibition; Anti-diabetic; Anti-hyperglycaemic; Benzenesulfonylurea/thiourea; Docking; NADPH