Design, Synthesis and Evaluation of Substituted 5-(2- methoxybenzylidene)-rhodanine Ester Analogs as Aldose Reductase Inhibitors

Author: Jyoti Pandey, Ritu Gilhotra and Arun K. Gupta

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Abstract

Aldose reductase (ALR) enzyme plays a significant role in conversion of excess amount of glucose into sorbitol in diabetic condition, inhibitors of which decrease the secondary complication of diabetes mellitus. The AR active site can adapts itself to bind firmly to special inhibitors; this happens together upon binding to the inhibitor’s hydrophobic, hydrophilic heads, and at the specificity pockets of AR, and capable to alter their nature through special conformational changes of the identical residues. Newer (E)-2-(5-(4-(benzoyloxy)-2-methoxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid and (E)-3-methoxy-4-((4-oxo-2-thioxothiazolidin-5-ylidene) methyl)phenyl benzoate derivatives were applied for molecular docking studies, synthesized, and these compound were evaluated for their ARI and antidiabetic activity. A docking study was also applied to envisage the interactions between the aldose reductase and designed series of compounds. The results of this present study mi

Keywords

Aldose Reductase Inhibitors, Docking, Diabetes, Substituted 5-(2-methoxybenzylidene)-rhodanine Ester Analogs.

Conclusion

Rhodanine and N-acetic acid rhodanine derivatives with various substitutions on benzylidene moiety were studied. A molecular docking study was performed using MVD to envisage the interactions between the aldose reductase active site and designed rhodanine series of compounds. Synthesized compound shows ARI activity in the range of 0.712 to 20.51 µM. The N-acetic acid analogs are more potent as compare to N-unsubstituted rhodanine analogs. In terminal phenyl ring at para position no substitution or fluoro substitution is favour for the activity while compound with bromo substitution on terminal phenyl ring shows minimum inhibition as compared to other analogs. The 3,4-dimethoxy substituted derivative proved to be the most active among these substituted compounds. In vivo study of N-acetic acid rhodanine derivatives were carried out by alloxan induced tail tipping method. Synthesized compound shows decrease in blood glucose level in the range of 28.80-10.64% after 3hrs while 39.28-18.2

References

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How to cite this article

Pandey, Jyoti, Gilhotra, Ritu and Gupta, Arun K. (2019). Design, Synthesis and Evaluation of Substituted 5-(2-methoxybenzylidene)-rhodanine Ester Analogs as Aldose Reductase Inhibitors. Biological Forum – An International Journal, 11(1): 217-221.