In silico investigation
of phytochemicals from Entada rheedii ethyl acetate leaf extract as potential inhibitors
of the Bcl-xL protein
Nair Lekshmy R., Duraipandian M. and Mini Gopinathan
Res. J. Biotech.; Vol. 21(1); 118-131;
doi: https://doi.org/10.25303/211rjbt1180131; (2026)
Abstract
Colorectal cancer (CRC) is a major global health concern and remains the second
leading cause of cancer-related mortality worldwide. A key hallmark of CRC progression
is the evasion of apoptosis, often facilitated by the overexpression of anti-apoptotic
proteins such as Bcl-xL. Inhibiting Bcl-xL is therefore a promising therapeutic
strategy, but conventional inhibitors are limited by toxicity and reduced efficacy
in Bcl-xL–overexpressing tumors. This study employed an in silico molecular docking
approach to investigate phytochemicals from the ethyl acetate leaf extract of Entada
rheedii as potential Bcl-xL inhibitors. The crystal structure of Bcl-xL (PDB ID:
2W3L) was retrieved from the Protein Data Bank, while the phytochemicals previously
identified via LC–MS QTOF were obtained from the PubChem database. SwissADME was
used to evaluate pharmacokinetic properties and AutoDock v1.5.7 was employed for
docking simulations.
Docking results revealed that spiraeoside exhibited the strongest binding affinity
(–7.8 kcal/mol), forming five hydrogen bonds and multiple hydrophobic interactions
with active site residues of Bcl-xL. Although spiraeoside violated some drug-likeness
rules due to its glycosylated structure, its binding strength and interaction profile
identify it as a promising lead compound. Other flavonoids such as apigenin, genistein,
luteolin and quercetin also demonstrated favorable pharmacokinetics and drug-like
properties. This study highlights the potential of E. rheedii phytochemicals, particularly
spiraeoside, as lead compounds for developing novel Bcl-xL inhibitors for colorectal
cancer therapy. Further in vitro and in vivo validation is warranted to establish
their biological efficacy and pharmacological feasibility.
