Development of novel pyrazolone derivatives as inhibitors of aldose reductase: An eco-friendly one-pot synthesis, experimental screening and in silico analysis

作者：Kadam Aparna; Dawane Bhaskar; Pawar Manisha; Shegokar Harshala; Patil Kapil; Meshram Rohan; Gacche Rajesh^*

来源：Bioorganic Chemistry, 2014, 53: 67-74.

DOI：10.1016/j.bioorg.2014.02.002

• Goat lens aldose reductase
• Pyrazolone derivatives
• Carbothioamide derivatives
• Polyethylene glycol (PEG-400)
• Paired potential analysis
• Virtual screening

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.

• 出版日期2014-4