Design Synthesis and Biological Evaluation of Some Novel Heterocyclic Compounds as Protein Tyrosine Phosphatase PTP Inhibitors

Abstract

Background: It has been found that inhibition of protein tyrosine phosphatase-1B (PTP1B) provide an enhancement of insulin sensitivity as well as decrease in obesity which is susceptible due to diet. Specific PTP1B inhibitors emerged as a new target for treatment of type-2 diabetes, obesity and also for cancer. Moreover, from literature survey and molecular docking it is observed that for selective PTP1B inhibition the some structural features are necessary like bidentate ligand, polar group should be substituted on the heterocyclic ring, aromatic ring that interacts with the hydrophobic pocket adjacent to catalytic site would provide selectivity and nitrogen atom interact with to Asp 48 of the enzyme. newlineResults and Discussion: All target compounds have been design by molecular docking and synthesized by name reaction like Biginelli reaction, Knovenagel condensation and common reaction like hydrolysis under acidic condition and all synthesized compounds were confirmed by their physical and spectral data. The synthesized compounds were evaluated for anti diabetic activity. Conclusion: The docking score of all compounds was in the range from 4.48 to 9.94. Moreover, the yield of synthesized compounds was in the range of 45% to 75% and their structures were established by spectral data. Moreover, Results of PTP-1B inhibition showed that substituted dihydropyrimidine and thiazolidine-4-one derivatives demonstrate moderate to high anti-diabetic activity. Among all the compounds, those with -OCH3, -CH3 Substitution was found to be more active. After conducting the in vitro studies it was observed that compounds RK4, RK5, RK7, RK12, RK13, RK15, RK19, RK20, RK24, RK25, RK29, RK30 having -OCH3, 3,4-OCH3 and CH3 substitution on phenyl ring in the basic moiety shows good anti diabetic activity and compound RK3, RK11, RK17, RK22, RK27 which is chloro substituted shows moderate anti diabetic activity newline