title: Development of novel pyrazolone derivatives as inhibitors of aldose reductase: an eco-friendly one-pot synthesis, experimental screening and in silico analysis.
abstract: Aldose reductase is the key enzyme of polypol pathway leading to accumulation of sorbitol. Sorbitol does not diffuse across the cell membranes easily and therefore accumulates within the cell, causing osmotic damage which leads to retinopathy (cataractogenesis), neuropathy and other diabetic complications. Currently, aldose reductase inhibitors like epalrestat, ranirestat and fidarestat are used for the amelioration of diabetic complications. However, such drugs are effective in patients having good glycemic control and less severe diabetic complications. In present study we have designed novel pyrazolone derivative and performed eco-friendly synthesis approach and tested the synthesized compounds as potential inhibitors of aldose reductase activity. Additional in silico analysis in current study indicates presence of highly conserved chemical environment in active site of goat lens aldose reductase. The reported data is expected to be useful for developing novel pyrazolone derivatives as lead compounds in the management of diabetic complications.
authors.affiliation: School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Kadam
authors.affiliation: School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Dawane
authors.affiliation: School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Pawar
authors.affiliation: School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Harshala
authors.initials: H
authors.lastname: Shegokar
authors.affiliation: School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Patil
authors.affiliation: School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India.
authors.forename: Rohan
authors.initials: R
authors.lastname: Meshram
authors.affiliation: School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded (MS), India. Electronic address: rngacche@rediffmail.com.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Gacche
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006041:Goats; D062105:Molecular Docking Simulation; D047069:Pyrazolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D047069:Pyrazolones; C038362:pyrazolone; D000449:Aldehyde Reductase
keywords: Carbothioamide derivatives; Goat lens aldose reductase; Paired potential analysis; Polyethylene glycol (PEG-400); Pyrazolone derivatives; Virtual screening