ANTIPROLIFERATIVE ACTIVITY OF N-BUTANOL FLORAL EXTRACT FROM BUTEA MONOSPERMA AGAINST HCT 116 COLON CANCER CELLS; DRUG LIKENESS PROPERTIES AND IN SILICO EVALUATION OF THEIR ACTIVE COMPOUNDS TOWARD GLYCOGEN SYNTHASE KINASE-3β/AXIN AND β-CATENIN/T-CELL FACTO

摘要

Objective: The aim was to study the inhibitory effect of n-butanol fraction of Butea monosperma floral extracts (NBF-BMFE) against HCT116 cells. Moreover, the drug-likeness properties and in silico evaluation of their active compounds toward glycogen synthase kinase-3β (GSK-3β)/Axin and β-catenin/T-Cell factor-4 (Tcf-4) complex proteins. Methods: The three-dimensional protein structures were incurred from RCSB protein data bank, and their active site amino acids predicted using CASTp server. Similarly, the NBE-BMFE phytochemicals were retrieved from PubChem Database then their absorption, distribution, metabolism, excretion, and toxicity (ADMET)-related descriptors were calculated by using the admetSAR along with ACD/i-lab software. The docking analysis was performed by using AutoDock 4.2. Concurrently, the NBF-BMFE were experimentally characterized by using liquid chromatography/mass spectrometry (LC/MS) besides their anticancer activity was assessed against HCT-116 human colon cancer cells. Results: The docking studies results showed that the NBF-BMFE phytochemicals showed good hydrogen bond interaction against GSK-3β/Axin (4B7T) and β-catenin/Tcf-4 (1JPW) complex proteins. Moreover, the in silico results of ADMET factors were also satisfying correspondingly. The LC/MS results revealed that the NBF-BMFE contains isocoreopsin, butrin and isobutrin as major compounds, and it has significant anticancer activity (?100 μM) against HCT-116 human colon cancer cells. Conclusion: Overall our results concluded that all the NBF-BMFE had significant inhibitory effect on HCT-116 cells plus good binding interaction with 4B7T and 1JPW, in specific isocoreopsin, butein and butin showed promising agents to develop as potent drug molecules against colorectal cancer.