Identification of 2-benzoxazolinone derivatives as lead against molecular targets of diabetic complications

Chemical Biology & Drug Design
Bhawna VyasOm Silakari

Abstract

Diabetic complications follow multiple pathophysiological pathways involving aldose reductase (ALR2)-mediated polyol pathway, advanced glycation end products (AGEs) and reactive oxygen species formation. Literature suggests ALR2 inhibitors such as epalrestat to possess significant potential in retinopathy and neuropathy. Thus, in this study, multiple pathophysiology directed molecules targeting ALR2, AGEs and free radicals formation were designed using in silico techniques. Initially, database was screened via in silico tools to obtain hits with affinity for the catalytic domain of ALR2. Additional focus was laid on the presence of structural attributes responsible for AGE's inhibitory and anti-oxidant potential. Out of obtained hits, 2-benzoxazolinone scaffold was selected and ten derivatives were synthesized accordingly. Finally, the synthesized molecules were evaluated for their ALR2 and AGEs inhibitory activities along with free radical scavenging potency.

References

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Aug 13, 2017·Journal of Molecular Graphics & Modelling·Navriti Chadha, Om Silakari

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Citations

Dec 31, 2019·Recent Patents on Drug Delivery & Formulation·Shalki ChoudharyOm Silakari
Apr 10, 2019·Oxidative Medicine and Cellular Longevity·Nidhi MahajanRajat Sandhir

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