PMID- 30396310
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20190215
IS  - 1532-4281 (Electronic)
IS  - 1079-9893 (Linking)
VI  - 38
IP  - 4
DP  - 2018 Aug
TI  - Zerumbone binding to estrogen receptors: an in-silico investigation.
PG  - 342-351
LID - 10.1080/10799893.2018.1531886 [doi]
AB  - Breast cancer is the most frequent malignancy among females worldwide. Estrogen 
      receptor (ER) mediate important pathophysiological signaling pathways induced by 
      estrogens, and is regarded as a promising target for the treatment of breast 
      cancer. Zerumbone (2,6,9,9-tetramethylcycloundeca-2,6,10-trien-1-one; ZER), a 
      chemical constituent present in the Zingiber zerumbet is known to exhibit 
      anti-breast cancer activity by modulating several proteins to induce apoptosis. 
      Medicinal chemists usually exploit lead compounds of natural origin to develop 
      molecules with improved pharmacological properties. Current study is intended to 
      utilize molecular modeling techniques to investigate the interaction of ZER with 
      estrogen receptors. AutoDock was used to predict the binding modes of ZER and 
      target receptors. Stability of the ZER-ER complex was verified by molecular 
      dynamics simulation using Desmond software. Docked ZER was further optimized by 
      density functional theory (DFT) using Gaussian09 program. Analysis of docked 
      conformations in terms of binding energy disclosed estrogen receptor-beta (ERbeta) as 
      more promising than estrogen receptor-alpha (ERalpha). Evaluation of MD trajectories of 
      ZER bound to both ERalpha and ERbeta showed appreciable stability with minimum Calpha-atom 
      root mean square deviation shifts. DFT based global reactivity descriptors such 
      as electron affinity, hardness, chemical potential, electronegativity and 
      electrophilicity index, calculated from the energies of highest occupied and 
      lowest unoccupied molecular orbitals underscored the electronic features 
      governing viability of the ZER for interaction with the target receptors. In 
      conclusion, these findings can be exploited to design and develop novel 
      anticancer agents based on the lead compound, ZER.
FAU - Eid, Eltayeb E M
AU  - Eid EEM
AD  - a Unaizah College of Pharmacy, Qassim University , Unaizah , Saudi Arabia.
FAU - Azam, Faizul
AU  - Azam F
AUID- ORCID: 0000-0002-2927-8167
AD  - a Unaizah College of Pharmacy, Qassim University , Unaizah , Saudi Arabia.
FAU - Hassan, Mahmoud
AU  - Hassan M
AD  - b Swiss Tropical & Public Health Institute, University of Basel , Switzerland.
FAU - Taban, Ismail M
AU  - Taban IM
AD  - c School of Biosciences, Cardiff University , Cardiff , United Kingdom.
FAU - Halim, Mohammad A
AU  - Halim MA
AD  - d Division of Computer-aided Drug Design , The Red-Green Research Center , BICCB 
      , Dhaka , Bangladesh.
AD  - e Institut Lumiere Matiere, Universite Lyon 1-CNRS, Universite de Lyon , 
      Villeurbanne Cedex , France.
LA  - eng
PT  - Journal Article
DEP - 20181105
PL  - England
TA  - J Recept Signal Transduct Res
JT  - Journal of receptor and signal transduction research
JID - 9509432
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Sesquiterpenes)
RN  - 471-05-6 (zerumbone)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Cell Proliferation/drug effects
MH  - Estrogen Receptor alpha/*chemistry/genetics
MH  - Estrogen Receptor beta/*chemistry/genetics
MH  - Female
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Sesquiterpenes/*chemistry/therapeutic use
OTO - NOTNLM
OT  - Breast cancer
OT  - density functionaltheory
OT  - docking
OT  - molecular dynamics
OT  - zerumbone
EDAT- 2018/11/07 06:00
MHDA- 2019/02/09 06:00
CRDT- 2018/11/07 06:00
PHST- 2018/11/07 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/11/07 06:00 [entrez]
AID - 10.1080/10799893.2018.1531886 [doi]
PST - ppublish
SO  - J Recept Signal Transduct Res. 2018 Aug;38(4):342-351. doi: 
      10.1080/10799893.2018.1531886. Epub 2018 Nov 5.