DOCKING STUDIES OF INDOLE ASSIMILATED PYRAZOLINE MOLECULAR HYBRIDS: DESIGN, SYNTHESIS AS ANTIINFLAMMATORY AGENTS AND ANTICANCER AGENTS

Abstract

A series of novel compounds (4a-4l) have been synthesized by Claisen-Schmidt condensation, Schiff’s base and Cyclization mechanism. All the molecule structures were affirmation by IR, ¹H NMR and Mass spectral data. The synthesized hybrids were screened for in vivo anti-inflammatory and invitro anticancer activities. Ant inflammatory activity was performed using carrageenan induced rat paw edema method using Diclofenac as standard drug. The anticancer activity has been assessing by using MTT assay against MCF7 and SKOV3 cell lines and Doxorubicin was used as reference standard. Among the compounds compound 4l exhibited the highest % inhibition of 98.4 when compared with the standard Diclofenac 94.2%.Compound 4f exhibited the lowest IC₅₀ at concentration of 20.01µg against MCF7 cell lines and 32.87µg against SKOV3 cell lines. The molecular docking studies was performed using the Ligprep tool of Schrodinger suite. This study revealed that novel thiazolidne-4-one-pyrazole hybrids(4a-4j) had good interaction with the active site of EGFR receptor. Among the docked compounds, dock score of the compounds ranged from from -3.186 to -5.212. The highest score was exhibited by 4f with -5.212 with Glide binding energy of -34.697 Kcal/mol.