Toward Understanding the Anticancer Activity of the Phytocompounds from Using Molecular Docking, in silico Toxicity and Dynamics Studies.

BACKGROUND

The Surinam cherry, belongs to the family Myrtaceae, an edible fruit-bearing medicinal plant with various biological properties. Several anticancer studies have been conducted on its essential oils while the non-essential oil compounds including phenolics, flavonoids, and carotenoids have not been fully investigated.

PURPOSE

Therefore, the study evaluated the in silico anticancer potentials of phenolic, flavonoid, and carotenoid compounds of against the MDM2 and Bcl-xL proteins, which are known to promote cancer cell growth and malignancy. The physicochemical parameters, validation, cytotoxicity, and mutagenicity of the polyphenols were determined using the SwissADME, pkCSM, ProTox-II, and vNN-ADMET online servers respectively. Lastly, the promising phytocompounds were validated using molecular dynamics (MD) simulation.

RESULTS

An extensive literature search resulted in the compilation of forty-four (44) polyphenols from . Top-rank among the screened polyphenols is galloylastragalin, which exhibited a binding energy score of -8.7 and -8.5 kcal/mol with the hydrophobic interactions (Ala93, Val141) and (Leu54, Val93, Ile99), as well as hydrogen bond interactions (Tyr195) and (Gln72) of the proteins Bcl-xL and MDM2 respectively. A complete in silico toxicity assessment revealed that the compounds, galloylastragalin, followed by myricetin, resveratrol, -Coumaroylquinic acid, and cyanidin-3-O-glucoside, were potentially non-mutagenic, non-carcinogenic, non-cytotoxic, and non-hepatotoxic. During the 120 ns MD simulations, the RMSF analysis of galloylastragalin- MDM2 (complex 1) and galloylastragalin- Bcl-xL (complex 2) showed the fewest fluctuations, indicating the conformational stability of the respective complexes.

CONCLUSION

This study has shown that polyphenol compounds of led by galloylastragalin, are potent inhibitors of the MDM2 and Bcl-xL cancer proteins. Thus, they may be considered as candidate polyphenols for further anticancer studies.