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
Abstract
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.
Keywords: Colorectal cancer, Butea monosperma, Absorption; distribution; metabolism; excretion and toxicity, Molecular docking, Glycogen synthase
kinase-3β/Axin, β-catenin/T-Cell factor-4.
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