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Synthesis of antihyperglycemic, α-glucosidase inhibitory, and DPPH free radical scavenging furanochalcones

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Abstract

A series of furanochalcone derivatives have been designed and synthesized. Molecular modeling studies were carried out to probe into the mechanism of binding of chalcone inhibitors and understand the structure–activity relationship to identify the contribution of scaffolds and groups in the synthesized analogs to biological activity. The three-dimensional model of α-glucosidase was constructed based on the crystal structure family 31 α-glycosidase (PDB 1XSI) using Modeller9v5. Docking of the inhibitors on the built homology model revealed interactions in the active site region mostly with Asp 252, Tyr254, Gln523, and Arg571. 2D-QSAR models were generated with CODESSA using Heuristic method. The best predictive model was generated using three descriptors that gave a correlation co-efficient (r 2) 0.9886 and cross-validate (r 2) 0.9338. The synthesized compounds were screened against the α-glucosidase inhibition and DPPH radical scavenging properties. All the synthetic compounds displayed varying degrees of α-glucosidase inhibitory and DPPH scavenging activities. Compound 8c was found most potent α-glucosidase inhibitor though; it could not display DPPH scavenging activity. When tested in vivo for antihyperglycemic activity in starch-loaded Wistar rats, 8c was equally effective in reducing time-dependent hyperglycemia as to the standard drug, Acarbose. Compound 8c may serve as an interesting compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.

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Acknowledgments

We are thankful to the Dr. J. S. Yadav, Director, IICT for his constant encouragement. The author R. R. Rao is also grateful to CSIR, New Delhi, for the award of Research Fellowship. P.B. thanks DST for the Women Scientist Fellowship.

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Authors and Affiliations

  1. Natural Products Laboratory, Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 607, India

    R. Ranga Rao, P. Prabhakar Reddy, K. Suresh Babu, G. Suresh & J. Madhusudana Rao

  2. Division of Pharmacology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 607, India

    Ashok K. Tiwari, A. Zehra Ali, K. Madhusudana & Sachin B. Agawane

  3. Molecular Modelling Group, Organic-I Division, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500 607, India

    Preethi Badrinarayan & G. Narahari Sastry

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  1. R. Ranga Rao
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Correspondence to J. Madhusudana Rao.

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Ranga Rao, R., Tiwari, A.K., Prabhakar Reddy, P. et al. Synthesis of antihyperglycemic, α-glucosidase inhibitory, and DPPH free radical scavenging furanochalcones. Med Chem Res 21, 760–774 (2012). https://doi.org/10.1007/s00044-011-9583-7

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