title: Synthesis and biological evaluation of new epalrestat analogues as aldose reductase inhibitors (ARIs).
abstract: Baylis-Hillman chemistry derived four series of new epalrestat analogues were synthesized. Three structural changes are introduced in these 39 new epalrestat analogues synthesized. All compounds were evaluated for their in vitro aldose reductase inhibitory (ALR) activity. Biological activity data indicates that compounds 6, 16, 19, 28 and 29 are potent and the activity is in the range of reference drug, epalrestat. Molecular modelling studies were performed to understand the binding interactions of these active molecules with the ALR protein. Molecular docking data indicates the key interactions of epalrestat were retained in some of the active compounds whereas some new interactions were noticed for other molecules. The modifications introduced on epalrestat have impact for developing a new-type of ALR inhibitor.
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Thatikonda Narendar
authors.initials: TN
authors.lastname: Reddy
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Mettu
authors.initials: M
authors.lastname: Ravinder
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Bagul
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Keerthi
authors.initials: K
authors.lastname: Ravikanti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research, Balanagar, Hyderabad 500037, India.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Bagul
authors.affiliation: Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Jagadeesh Babu
authors.initials: JB
authors.lastname: Nanubolu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research, Balanagar, Hyderabad 500037, India.
authors.forename: Kolupula
authors.initials: K
authors.lastname: Srinivas
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Banerjee
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500607, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research, Balanagar, Hyderabad 500037, India. Electronic address: jrao@iict.res.in.
authors.forename: Vaidya Jayathirtha
authors.initials: VJ
authors.lastname: Rao
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018360:Crystallography, X-Ray; D048909:Diabetes Complications / Q000188:drug therapy / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase
keywords: Aldose reductase inhibitors; Baylis–Hillman reaction; Crystal structure; Epalrestat analogues; Molecular docking; Rhodanine compounds