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

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 a-glucosidase was constructed based on the crystal structure family 31 a-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 a-glucosidase inhibition and DPPH radical scavenging properties. All the synthetic compounds displayed varying degrees of a-glucosidase inhibitory and DPPH scavenging activities. Compound 8c was found most potent a-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.

Diversity-Oriented Synthesis of Natural-Product-like Libraries Containing a 3-Methylbenzofuran Moiety for the Discovery of New Chemical Elicitors

“…The synthesis of angular 3‐methylfuranochalcones 11 was accomplished from commercially available starting materials in the presence of bases through Claisen–Schmidt condensation (Table ) . First, we investigated the effect of bases on the reactions of 8 with benzaldehyde.…”

“…The synthesis of angular 3-methylfuranochalcones 11 was accomplished from commerciallya vailables tarting materials in the presence of bases through Claisen-Schmidt condensation ( Table 2). [14] First, we investigated the effect of bases on the reactions of 8 with benzaldehyde.I tw as found that 5equivalents of NaOH can hardly catalyzet he reaction (yield < 5%). KOH gave 57 %y ield of the desired product 11 a.F urther screening of other bases afforded av ery good yield (82 %) of 11 a,a nd NaH was proved to be optimal for this transformation.…”

“…GeneralProcedure for the Synthesis of Angular3 -Methylfuranoflavones (14) Am ixture of anhydrous DMSO (5.2 mL) and NaH (36.4 mmol, 60 % dispersion in mineral oil) in anhydrous toluene (60 mL) was heated at 80 8Cu nder N 2 for 2h.T he solution was cooled to 40 8C, and as olution of 9 (7.2 mmol) in anhydrous toluene (8 mL) was added dropwise to the stirred solution. The reaction mixture was then stirred at 40 8Cf or 1h,d iluted with diethyl ether (75 mL), and quenched with as aturated solution of NH 4 Cl (60 mL).…”

“…Therefore, we predict that the 3‐methylfuran scaffold is an important factor in the activity of these molecules, and we expect to find chemical elicitors by synthesizing NP‐like libraries containing the 3‐methylfuran moiety. Furthermore, coumarin, chalcone, flavone, flavonol, isoflavone and isoquinolinone are six naturally occurring compounds that have exhibited a variety of biological activities. Inspired by these NPs and their inherent biological activities, we designed a divergent synthetic pathway to synthesize 88 NP‐like compounds based on a key 3‐methylfuran core obtained from available starting material cyclohexane‐1,3‐diketone (Scheme ) .…”