Molecular docking, Synthesis, Computational Studies and In-vitro evaluation of 7-Substituted-2-Pyrimidinyl Chromen-4-one derivatives

Abstract

Design and synthesis of 7-substituted-2-pyrimidinyl chromen-4-one derivatives as selective Cyclooxygenase-2 inhibitors (1) Method: The compounds were designed using molecular hybridization technique, docking studies was performed using Autodock Vina, compounds having higher affinity than celecoxib were selected and synthesized followed by spectral characterization. The synthesized derivatives (1a, 1b, 2-9) were subjected to ADMET and PASS prediction studies. In vitro antioxidant potential was assayed by DPPH method and in vitro anti-inflammatory activity was assessed by protein denaturation method. (2)Result: Compounds under study have been found to exhibit good to moderate anti-inflammatory activity. Among these, compounds 1a, 1b and 4 exhibited maximum anti-inflammatory activity which is comparable to the activity of Diclofenac sodium. Compound 1a and 4 are found to be the most potent antioxidant with a remarkable IC50 value of 6.99 and 7.25 respectively, which is a little less than the standard drug, ascorbic acid, (IC50=6.94). In addition, a comparative examination of calculated Lipinski’s parameters reveals that all the compounds have the tendency to be orally bioavailable. PASS studies also show that certain compounds also have higher probability of anti-neoplastic activity. (3) Conclusion: Based on the outcomes, compounds 1a, 1b, 3, 4 and 8 can act as novel leads for the development of COX-2 inhibitors showing potent anti-inflammatory and antioxidant activity which can have lesser GI side effects and can be used in chronic disorders.