Molecular Networking, Docking, and Biological Evaluation of Licarin A from Myristica fragrans as a Potential Cancer Chemopreventive Agent

Currently, clinically available cancer chemopreventive drug options are limited to mostly tamoxifen and its derivatives, such as raloxifene, and approved specifically for breast cancer. Thus, the availability of chemopreventive drug molecules for other types of malignant cancers would be desirable....

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2024-10, Vol.29 (20), p.4919
Main Authors: Blanco Carcache, Peter J, Castro-Dionicio, Ines Y, Mirtallo Ezzone, Nathan P, Salinas-Arrellano, Eric D, Bahar, Joshua, Clinton, Steven K, Kinghorn, A Douglas
Format: Article
Language:English
Subjects:
Amino acids
Animals
Anticarcinogenic Agents - chemistry
Anticarcinogenic Agents - pharmacology
Cancer
cancer chemoprevention
Care and treatment
Cell Line, Tumor
Chromatography
Cytotoxicity
docking
Drug approval
Drug dosages
Humans
lack of toxicity
licarin A
Lignans - chemistry
Lignans - pharmacology
Mice
Molecular Docking Simulation
molecular networking
Myristica - chemistry
Natural products
Oxidative stress
Phosphorylation
Phytochemicals
Prevention
Prostate cancer
Tamoxifen
Toxicity
Vitamin C
Zebrafish
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Summary:Currently, clinically available cancer chemopreventive drug options are limited to mostly tamoxifen and its derivatives, such as raloxifene, and approved specifically for breast cancer. Thus, the availability of chemopreventive drug molecules for other types of malignant cancers would be desirable. In previous reports, the arils of (mace) have been found to exhibit cancer chemopreventive activity. Therefore, the purpose of the present study was to identify a natural product from this species with potential chemopreventive activity guided by chemoinformatic sample analysis via Global Natural Products Social (GNPS) molecular networking and molecular docking. The neolignan licarin A ( ) was identified as a potential chemopreventive constituent, and subsequently submitted to several in vitro bioassays and a zebrafish toxicity evaluation. In this work, afforded superior phosphoNF- Bp65 phosphorylation activity in DU-145 prostate cancer cells compared to isoliquiritigenin ( ), which was used as a natural product chemopreventive control. Both and showed a longer-lasting reduction in cellular stress in a cell oxidative stress real-time dose-response assay than the positive control using Hepa1c1c7 mouse hepatoma cells. In addition, displayed similar activities to , while also being less toxic to zebrafish ( ) than both this chalcone and the clinically used chemopreventive drug tamoxifen.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules29204919