PMID- 29925285
OWN - NLM
STAT- MEDLINE
DCOM- 20181226
LR  - 20181226
IS  - 1537-6524 (Electronic)
IS  - 1537-6516 (Linking)
VI  - 28
IP  - 9
DP  - 2018 Nov
TI  - In silico molecular interaction of bisphenol analogues with human nuclear 
      receptors reveals their stronger affinity vs. classical bisphenol A.
PG  - 660-669
LID - 10.1080/15376516.2018.1491663 [doi]
AB  - BACKGROUND: Bisphenol A (BPA) is known for endocrine disrupting activity. In 
      order to replace BPA, a number of bisphenol analogues have been designed. 
      However, their activity profile is poorly described and little information exists 
      about their endocrine disrupting potential and interactions with nuclear 
      receptors. An understanding of such interaction may unravel mechanism of their 
      molecular action and provide valuable inputs for risk assessment. BPA binds and 
      activates peroxisome proliferator-activated receptors (PPARs) and retinoid X 
      receptors (RXRs) which act as transcription factors and regulate genes involved 
      in glucose, lipid, and cholesterol metabolism and adipogenesis. METHODS: We 
      studied binding efficiency of 18 bisphenol analogues and BPA with human PPARs and 
      RXRs. Using Maestro Schrodinger 9.4, docking scores of bisphenols were compared 
      with the known endogenous and exogenous ligands of hPPARs and hRXRs. RESULTS: BPA 
      showed good binding efficiency. Several analogues also showed higher binding 
      efficiency than BPA. BPPH which has high tendency to be absorbed in tissues 
      showed the strongest binding with hPPARalpha, hPPARbeta, hPPARgamma, and hRXRalpha whereas two 
      of the most toxic bisphenols, BPM and BPAF showed strongest binding with hRXRbeta 
      and hRXRgamma. CONCLUSIONS: Some of the bisphenol analogues showed a stronger binding 
      affinity with PPAR and RXR compared to BPA implying that BPA substitutes may not 
      be fully safe and chemico-biological interactions indicate their toxic potential. 
      These results may also serve to plan further studies for determining safety 
      profile of bisphenol analogues and be helpful in risk characterization.
FAU - Sharma, Shikha
AU  - Sharma S
AD  - a Department of Medical Elementology & Toxicology , Jamia Hamdard (Hamdard 
      University) , New Delhi , India.
FAU - Ahmad, Shahzad
AU  - Ahmad S
AD  - a Department of Medical Elementology & Toxicology , Jamia Hamdard (Hamdard 
      University) , New Delhi , India.
FAU - Khan, Mohemmed Faraz
AU  - Khan MF
AD  - b Department of Pharmaceutical Chemistry , Jamia Hamdard (Hamdard University) , 
      New Delhi , India.
FAU - Parvez, Suhel
AU  - Parvez S
AD  - a Department of Medical Elementology & Toxicology , Jamia Hamdard (Hamdard 
      University) , New Delhi , India.
FAU - Raisuddin, Sheikh
AU  - Raisuddin S
AUID- ORCID: 0000-0003-0913-8906
AD  - a Department of Medical Elementology & Toxicology , Jamia Hamdard (Hamdard 
      University) , New Delhi , India.
LA  - eng
PT  - Journal Article
DEP - 20181005
PL  - England
TA  - Toxicol Mech Methods
JT  - Toxicology mechanisms and methods
JID - 101134521
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Phenols)
RN  - 0 (Retinoid X Receptors)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Benzhydryl Compounds/*chemistry/toxicity
MH  - Endocrine Disruptors/*chemistry/toxicity
MH  - Humans
MH  - *Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Peroxisome Proliferator-Activated Receptors/*chemistry
MH  - Phenols/*chemistry/toxicity
MH  - Protein Binding
MH  - Retinoid X Receptors/*chemistry
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Endocrine disrupting chemicals
OT  - bisphenol analogues
OT  - nuclear receptors
OT  - risk characterization
EDAT- 2018/06/22 06:00
MHDA- 2018/12/27 06:00
CRDT- 2018/06/22 06:00
PHST- 2018/06/22 06:00 [pubmed]
PHST- 2018/12/27 06:00 [medline]
PHST- 2018/06/22 06:00 [entrez]
AID - 10.1080/15376516.2018.1491663 [doi]
PST - ppublish
SO  - Toxicol Mech Methods. 2018 Nov;28(9):660-669. doi: 10.1080/15376516.2018.1491663. 
      Epub 2018 Oct 5.