SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF SOME NEW HETEROCYCLIC DERIVATIVES OF CHALCONE AS ANTIHYPERGLYCEMIC AGENTSAbstract
Protein tyrosine phosphatase 1B (PTP1B) is an important target for diabetes since inhibition of PTP1B offers therapeutic benefits in insulin-resistant diabetes. Considering this fact in present investigation various heterocyclic derivatives of chalcone were synthesized and evaluated for their PTP1B inhibitory activity as antihyperglycemic agents. Heterocyclic derivatives; isoxazoline (II A-II E), and pyrazoline (III A – III E / VIA-VIC) were synthesized through cyclization of chalcone intermediates and structures of final compounds were established using various spectral analysis techniques such as; IR, 1H-NMR and mass. Compounds were screened for their antihyperglycemic activity using sucrose loaded diabetic model. Isoxazoline derivatives offered potent antihyperglycemic response than correspondence pyrazoline derivatives. Compounds bearing isoxazoline ring II A and II E showed maximum % fall of blood glucose level than control group which was comparable to the standard drug metformin. The newer compounds VIA, VIB, and VIC also evaluated for their anti-hyperglycemic activities, compound VIC showed appreciable response (62.5% antihyperglycemic activity). The result of biological activity was also anticipated by molecular docking study which was performed to confirm PTP1B inhibitory potential of synthesized derivatives using molegro virtual docker (MVD) software.