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

Autor: Blanco Carcache PJ; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA., Castro-Dionicio IY; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA., Mirtallo Ezzone NP; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA., Salinas-Arrellano ED; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA., Bahar J; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA., Clinton SK; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.; Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA., Kinghorn AD; The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.; Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2024 Oct 17; Vol. 29 (20). Date of Electronic Publication: 2024 Oct 17.
DOI: 10.3390/molecules29204919
Abstrakt: 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 Myristica fragrans (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 ( 1 ) was identified as a potential chemopreventive constituent, and subsequently submitted to several in vitro bioassays and a zebrafish toxicity evaluation. In this work, 1 afforded superior phosphoNF- κ Bp65 phosphorylation activity in DU-145 prostate cancer cells compared to isoliquiritigenin ( 2 ), which was used as a natural product chemopreventive control. Both 1 and 2 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, 1 displayed similar activities to 2 , while also being less toxic to zebrafish ( Danio rerio ) than both this chalcone and the clinically used chemopreventive drug tamoxifen.
Databáze: MEDLINE
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