Potential Activity of Fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. Seeds as Estrogen Receptor Antagonist Based on Cytotoxicity and Molecular Modelling Studies

International Journal of Molecular Sciences

Muchtaridi Muchtaridi²  Muhammad Yusuf¹  Ajeng Diantini²  Sy Bing Choi¹  Belal O. Al-Najjar¹  Jerry V. Manurung²  Anas Subarnas²  Tri H. Achmad³  Savitri R. Wardhani³ 

[1] Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Pulau Pinang, Malaysia; E-Mails:;Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jln. Raya Bandung Sumedang KM. 21, Jatinangor, West Java 45363, Indonesia; E-Mails:;Faculty of Medicine, Universitas Padjadjaran, Jln. Raya Bandung-Sumedang KM. 21, Jatinangor, West Java 45363, Indonesia; E-Mails:

关键词: fevicordin A;    estrogen receptor;    pharmacophore;    molecular dynamics;    Phaleria macrocarpa;   

DOI  :  10.3390/ijms15057225

来源: mdpi

【 摘 要 】

Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC₅₀ value of 6.4 μM. At 11.2 μM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.

【 授权许可】

CC BY   
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