title: Design and synthesis of chiral 2H-chromene-N-imidazolo-amino acid conjugates as aldose reductase inhibitors.
abstract: Aldose reductase (ALR2) inhibitors provide a viable mode to fight against diabetic complications. ALR2 exhibit plasticity in the active site vicinities and possible shifts in the nearby two supporting alpha helices. Therefore, a novel series of amino acid conjugates of chromene-3-imidazoles (13-15) were designed and synthesized based on natural isoflavonoids. The compounds were identified on the basis of spectral (1H NMR,13C NMR and MS) data and tested in vitro for ALR2 inhibitory activity with an IC50value ranges from 0.031 ± 0.082 μM to 4.29 ± 0.55 μM. Our in silico and biochemical studies confirmed that 15e has the best inhibition activity among the synthesized compounds with a high selective index against the Aldehyde reductase (ALR1). Supplementation of 15e to STZ induced rats decreased the blood glucose levels and delayed the progression of cataract in a dose-dependent manner. The present study thus provides novel series of compounds with a promising inhibitor to prevent or delay the cataract progression.
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad, 500 007, India.
authors.forename: Gudipudi
authors.initials: G
authors.lastname: Gopinath
authors.affiliation: Department of Zoology, Osmania University, Hyderabad, 500 007, India.
authors.forename: Venu
authors.initials: V
authors.lastname: Sankeshi
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, 500 007, India.
authors.forename: Shaym
authors.initials: S
authors.lastname: Perugu
authors.affiliation: Department of Genetics, Drug Design & Molecular Medicine Lab, Osmania University, Hyderabad, 500 007, India.
authors.forename: Malini D
authors.initials: MD
authors.lastname: Alaparthi
authors.affiliation: Department of Genetics, Drug Design & Molecular Medicine Lab, Osmania University, Hyderabad, 500 007, India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad, 500 007, India.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Pasala
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad, 500 007, India.
authors.forename: Prasad Rao
authors.initials: PR
authors.lastname: Chittineni
authors.affiliation: Department of Chemistry, Osmania University, Hyderabad, 500 007, India. Electronic address: gldkrupa@gmail.com.
authors.forename: G L David
authors.initials: GLD
authors.lastname: Krupadanam
authors.affiliation: Department of Genetics, Drug Design & Molecular Medicine Lab, Osmania University, Hyderabad, 500 007, India. Electronic address: drsomeswar@osmania.ac.in.
authors.forename: Someswar R
authors.initials: SR
authors.lastname: Sagurthi
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D020134:Catalytic Domain; D002386:Cataract / Q000188:drug therapy / Q000209:etiology; D048909:Diabetes Complications / Q000188:drug therapy; D004195:Disease Models, Animal; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D001578:Benzopyrans; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; C117197:imidazolone; D000449:Aldehyde Reductase
keywords: 2H-chromene-3-carboxylicacids; Aldose reductase inhibitor; Amino acids; Diabetic complications; Imidazole; Molecular docking