Agonist and antagonist recognition studies for oestrogen receptor by molecular dynamics simulation

Li, Wenming; Li, Xiaobo; Sun, Su-Xia; Liang, Jing; Wang, Run‐Ling; Wang, Shuqing

doi:10.1080/08927022.2012.717281

Cited by 10 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sigma bond interactions with Met 421 was observed in Compounds 1, 3, 4, 5 & 9 of B1 series only. Wen Ming Li [17] concluded from his study of molecular dynamics for the ER-Diethylstilbesterol and ER-4-hydroxy tamoxifen complexes: a) The residue of Glu353 participates in both agonist and antagonist recognition. b) His524 residue only takes part in the agonist recognition.…”

Section: Experiments and Detection Methodsmentioning

confidence: 99%

Insilico Docking Study of Isoxazole Indole Linked Resorcinol Derivatives as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs

Iyer

Khare²,

Pandey

2022

Drug Res (Stuttg)

View full text Add to dashboard Cite

A series of 9 compounds with isoxazole-indole-γ-resorcylic acid scaffold, segregated into B1 & A1 series, wherein, B1 comprises compounds:1,3,4,5, & 9 and A1comprises compounds: 2,6,7, & 8 , on the basis of variable substituents at the indole , resorcinol and isoxazole end of the scaffold as in Fig. 1, were designed and docked with human estrogen receptor:1ERRα. The binding affinity (BA) and the interacting amino acids compared with reference selective estrogen receptor modulators (SERMs) such as Raloxifene, Estradiol, Bazedoxifene, Bisphenol, Genistein, Daidzein, Ormiloxifene,Tamoxifen,6-hydroxy-naphthalen-2yl-benzo(D)-isoxazol-6-ol(1)(WAY-397) using PyRx software and their ADME properties predicted with SWISS ADME online tool. Significant similarities and minor differences in the binding pattern between the key interacting aminoacids such as Arg 394,Glu 353, Asp 351, Leu 346, Leu 525, Trp 383,Phe 404 ,Ala 350, Leu 387, Met 421 responsible for ER agonist/antagonist activity found in the binding cavity of a 1 Errα -Bazedoxifene/1 Errα -raloxifene/1 Errα -estradiol docked complex AND 1 Errα -isoxazole-indole- resorcinol docked complex indicate their promising potential to serve as potent ER agonists in bone or ER antagonists against breast cancer and other cancer diseases. The Compounds with Highest BA is of the order: BA (A1series)>B1 series & BA(6)=BA(8)>BA(7)>BA(2)>BA(9)=BA(1)>BA(3)>BA(4)=BA(5)

show abstract

Section: Experiments and Detection Methodsmentioning

confidence: 99%

Insilico Docking Study of Isoxazole Indole Linked Resorcinol Derivatives as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs

Iyer

Khare²,

Pandey

2022

Drug Res (Stuttg)

View full text Add to dashboard Cite

show abstract

“…[30] In agonist behaviour, His524 emerged as the key residue, while in antagonist recognition, the key residues included Met343, Leu346, Thr347, and Asp351. [30] With the docking results, OHT and three ester derivatives 1-3 demonstrated a favourable binding affinity with 3ERT compared to 1GWR, suggesting a potential antagonist when interacting with 3ERT. Conversely, E 2 and curcumin exhibited Table 1.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…[29] Molecular dynamics simulations of ERα/ diethylstilbestrol and ERα/OHT revealed the bi-faceted effect of Glu353 in recognizing both agonists and antagonists. [30] In agonist behaviour, His524 emerged as the key residue, while in antagonist recognition, the key residues included Met343, Leu346, Thr347, and Asp351. [30] With the docking results, OHT and three ester derivatives 1-3 demonstrated a favourable binding affinity with 3ERT compared to 1GWR, suggesting a potential antagonist when interacting with 3ERT.…”

Section: Molecular Dockingmentioning

confidence: 99%

Design, Synthesis, Cytotoxic Evaluation, and Molecular Docking of New Alkyl Triphenylphosphonium Curcumin Derivatives

Hoang Dang,

Hoai Tran,

Huu Le

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Despite the previous anticancer effects of curcumin against various cancer cell lines, in vitro, pre–clinical, and clinical studies have faced constraints, particularly at high doses. Therefore, the mitochondria–targeted approach represents a promising trend in cancer drug development. This study successfully synthesized three new alkyl triphenylphosphonium ester curcumin derivatives (1–3) with good yield. They demonstrated cytotoxicity against MCF‐7 cells with IC50 values of 49.72, 62.57, and 91.73 μM, respectively. These values indicated higher potency than free curcumin (IC50>100 μM). Molecular docking studies of curcumin and three derivatives 1–3 with two estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro–proliferative function), were carried out. These domains are important targets in hormone–dependent anticancer strategies. The favourable docking scores and key residue interactions suggested that these derivatives could be the potential antagonists. Three synthesized alkyl–TPP+ curcumin ester derivatives (1–3) demonstrated more potent cytotoxic efficacy than curcumin, particularly against the human MCF‐7 breast cancer cell line. In addition, molecular docking studies suggested their potential as antagonists of ERα. The in silico ADMET data of three derivatives (1–3) showed compliance with the Lipinski rule and demonstrated their absorption, distribution, metabolism, and excretion properties.

show abstract

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti‐Breast Cancer Agents

Tran,

Le,

Nguyen

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria‐targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1–8) with good yield in this study. Seven compounds (1–3, 5–8) showed greater cytotoxic potency against the human MCF‐7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone‐dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro‐proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

show abstract

Agonist and antagonist recognition studies for oestrogen receptor by molecular dynamics simulation

Cited by 10 publications

References 33 publications

Insilico Docking Study of Isoxazole Indole Linked Resorcinol Derivatives as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs

Insilico Docking Study of Isoxazole Indole Linked Resorcinol Derivatives as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs

Design, Synthesis, Cytotoxic Evaluation, and Molecular Docking of New Alkyl Triphenylphosphonium Curcumin Derivatives

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti‐Breast Cancer Agents

Contact Info

Product

Resources

About