Int. J. Mol. Sci. 2014, 15(5), 7225-7249; doi:10.3390/ijms15057225
Article

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

1,†,* email, 2,†email, 1email, 2email, 2email, 1email, 1email, 3email, 3email and 2,4,* email
Received: 22 November 2013; in revised form: 10 January 2014 / Accepted: 15 January 2014 / Published: 25 April 2014
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: fevicordin A; estrogen receptor; pharmacophore; molecular dynamics; Phaleria macrocarpa
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MDPI and ACS Style

Muchtaridi, M.; Yusuf, M.; Diantini, A.; Choi, S.B.; Al-Najjar, B.O.; Manurung, J.V.; Subarnas, A.; Achmad, T.H.; Wardhani, S.R.; Wahab, H.A. Potential Activity of Fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. Seeds as Estrogen Receptor Antagonist Based on Cytotoxicity and Molecular Modelling Studies. Int. J. Mol. Sci. 2014, 15, 7225-7249.

AMA Style

Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, Subarnas A, Achmad TH, Wardhani SR, Wahab HA. 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. 2014; 15(5):7225-7249.

Chicago/Turabian Style

Muchtaridi, Muchtaridi; Yusuf, Muhammad; Diantini, Ajeng; Choi, Sy B.; Al-Najjar, Belal O.; Manurung, Jerry V.; Subarnas, Anas; Achmad, Tri H.; Wardhani, Savitri R.; Wahab, Habibah A. 2014. "Potential Activity of Fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. Seeds as Estrogen Receptor Antagonist Based on Cytotoxicity and Molecular Modelling Studies." Int. J. Mol. Sci. 15, no. 5: 7225-7249.

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