In:
Clinical Cancer Drugs, Bentham Science Publishers Ltd., Vol. 8, No. 1 ( 2021-03), p. 57-66
Abstract:
In the last decades, growing evidence demonstrates interest in phytoestrogen
intake to modulate targets in different types of cancer. Plant lignans have proven efficacious in blocking estrogen receptors of breast cancer cells. Among them, four phytoestrogen lignans: pinoresinol,
matairesinol, lariciresinol, and secoisolariciresinol have been most studied. However, available studies have mostly dealt with the anti-cancer effects of groups of lignans in certain foods
or plants and the effects of specific lignans, especially from a molecular interaction viewpoint, have been rarely addressed in the literature. Objective: We aimed to in silico predict pharmacological properties, binding ability and binding
strength of pinoresinol, matairesinol, lariciresinol and secoisolariciresinol as possible inhibitors of estrogen receptor alpha which is the most important biomarker in breast cancer. Methods: Firstly, we evaluated the pharmacological properties of four lignans using SwissADME.
Then we investigated the ligand-receptor interactions of these molecules as positively appraised ligands for ER-positive breast cancer targeted therapy using docking method. We finally compared
the inhibitory effect possibility of the lignans against endoxifen which is the active metabolite of tamoxifen. Results: The best binding affinity of endoxifen, matairesinol, pinoresinol, lariciresinol and secoisolariciresinol
were respectively -9.2, -7.5, -6.7, -6.7, -5.8 kcal/mol. In the meantime, matairesinol showed a minimum binding energy than other studied lignans in addition to the most similar interactions
to endoxifen with conserved domain residues of the active site pocket in Leu:391, Ala:350, Met:421, and Phe:404. Conclusion: Among the studied lignans, matairesinol showed favorable pharmacokinetics and
drug-likeliness properties, the least binding energy as well as the most common interactions in conserved residues of the active site pocket with estrogens. This makes it a molecule with low number
of nonspecific interactions, better target selectivity, and hence fewer side effects. Thus, our results introduce matairesinol as a possibly effective anti-estrogen receptor inhibitor candidate.
Type of Medium:
Online Resource
ISSN:
2212-697X
DOI:
10.2174/2212697X08666210923123117
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2021
Bookmarklink