Structure-based drug design, synthesis, In vitro, and In vivo biological evaluation of indole-based biomimetic analogs targeting estrogen receptor-α inhibition

2019 ◽  
Vol 166 ◽  
pp. 281-290 ◽  
Author(s):  
Moataz S. Hendy ◽  
Aya A. Ali ◽  
Lubna Ahmed ◽  
Reham Hossam ◽  
Alaa Mostafa ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Drug Design ◽  
Estrogen Receptor Α ◽  
Biological Evaluation ◽  
Structure Based Drug Design ◽  
Design Synthesis

Design, Synthesis, and in Vitro Biological Evaluation of Small Molecule Inhibitors of Estrogen Receptor α Coactivator Binding

2004 ◽  
Vol 47 (3) ◽  
pp. 600-611 ◽  
Author(s):  
Alice L. Rodriguez ◽  
Anobel Tamrazi ◽  
Margaret L. Collins ◽  
John A. Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Estrogen Receptor Α ◽  
Biological Evaluation ◽  
Design Synthesis

scholarly journals Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole Bearing Pyridine Moiety

2019 ◽  
pp. 300-307
Author(s):  
Asma D. Ambekari ◽  
Shrinivas K. Mohite
Keyword(s):  
Antimicrobial Activity ◽  
Mass Spectra ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Pyridine Moiety ◽  
Anti Inflammatory ◽  
Physicochemical Data ◽  
Synthesis And Biological Evaluation

Series of novel substituted Synthesis of N-{[5-(substituted)-1,3,4-oxadiazole-2-yl] carbamothioyl} derivatives containing 1,3,4-oxadiazole moiety were synthesized by microwave as a green chemistry method and conventional method by using pyridine 3- carboxylic acid as a starting material. The structures of the synthesized compounds were characterized by physicochemical data, IR, Mass spectra and 1HNMR. All the newly synthesized compound screened for their antimicrobial and In-vivo and In-vitro Anti-inflammatory studies. Anti-inflammatory studies revealed that compound 4f showed significant in-vivo and in-vitro anti-inflammatory activity as well potent antimicrobial activity.

scholarly journals Comparative study of estrogen receptor α, β mRNA expressions of endometriosis and normal endometrium in women and analysis of potential synthetic anti-estrogens in silico

2018 ◽  
Vol 91 (2) ◽  
Author(s):  
Eldafira Eldafira ◽  
Abinawanto Abinawanto ◽  
Luthfiralda Sjahfirdi ◽  
Asmarinah Asmarinah ◽  
Purnomo Soeharso ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mrna Expression ◽  
Estrogen Receptor Α ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Endometrium ◽  
Pcr Method ◽  
Genetic And Environmental Factors

Endometriosis is a multifactorial disease in which genetic and environmental factors interact causing its pathogenesis. The aim of this study was to investigate the expression pattern of estrogen receptor α (ERα) and β (ERβ) in endometriosis patients compared to normal endometrioum (n=18) as a control by using Quantitative Real Time PCR method. Moreover, we also measured serum estradiol levels of endometriosis patients in the proliferation phase of the menstrual cycle using the enzyme-linked immunosorbent assay method. The mRNA expression of ERβ was significantly higher in the endometriosis group compared to control, and the result of t-test showed that were significantly different (P<0.05). Overexpression of ERβ in endometriosis was likely to have other significant important impacts in the pathology of endometriosis that allowed ERβ to stimulate prostaglandin production in endometriosis tissue and cells. Estradiol content did not correlate with the ERα expression, and it is weakly correlated with ERβ mRNA expression. Molecular docking analysis showed that ERα and ERβ have different binding interactions with synthetic antiestrogens, whereas the best inhibitor was Ral2 to ERα and Aco1 to ERβ. Thus, both inhibitors could be used as leads in further investigation of ERα, ERβ inhibitory activities in vitro and in vivo.

scholarly journals Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259008
Author(s):  
Leandro da Costa Clementino ◽  
Guilherme Felipe Santos Fernandes ◽  
Igor Muccilo Prokopczyk ◽  
Wilquer Castro Laurindo ◽  
Danyelle Toyama ◽  
...  
Keyword(s):  
Parasite Burden ◽  
Peritoneal Macrophages ◽  
Biological Evaluation ◽  
Antileishmanial Activity ◽  
Dual Effect ◽  
Design Synthesis ◽  
Murine Peritoneal Macrophages ◽  
Synthesis And Biological Evaluation

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

scholarly journals Sexually Dimorphic Effect of Genistein on Hypothalamic Neuronal Differentiation in Vitro

2019 ◽  
Vol 20 (10) ◽  
pp. 2465 ◽  
Author(s):  
Marilena Marraudino ◽  
Alice Farinetti ◽  
Maria-Angeles Arevalo ◽  
Stefano Gotti ◽  
GianCarlo Panzica ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Sex Differences ◽  
Estrogen Receptors ◽  
Estrogen Receptor Α ◽  
Neuronal Cultures ◽  
Sexually Dimorphic ◽  
Hypothalamic Neurons ◽  
Estrogen Receptor Antagonists

Developmental actions of estradiol in the hypothalamus are well characterized. This hormone generates sex differences in the development of hypothalamic neuronal circuits controlling neuroendocrine events, feeding, growth, reproduction and behavior. In vitro, estradiol promotes sexually dimorphic effects on hypothalamic neuritogenesis. Previous studies have shown that developmental actions of the phytoestrogen genistein result in permanent sexually dimorphic effects in some behaviors and neural circuits in vivo. In the present study, we have explored if genistein, like estradiol, affects neuritogenesis in primary hypothalamic neurons and investigated the estrogen receptors implicated in this action. Hypothalamic neuronal cultures, obtained from male or female embryonic day 14 (E14) CD1 mice, were treated with genistein (0.1 µM, 0.5 µM or 1 µM) or vehicle. Under basal conditions, female neurons had longer primary neurites, higher number of secondary neurites and higher neuritic arborization compared to male neurons. The treatment with genistein increased neuritic arborization and the number of primary neurites and decreased the number of secondary neurites in female neurons, but not in male neurons. In contrast, genistein resulted in a significant increase in primary neuritic length in male neurons, but not in female neurons. The use of selective estrogen receptor antagonists suggests that estrogen receptor α, estrogen receptor β and G-protein-coupled estrogen receptors are involved in the neuritogenic action of genistein. In summary, these findings indicate that genistein exerts sexually dimorphic actions on the development of hypothalamic neurons, altering the normal pattern of sex differences in neuritogenesis.

scholarly journals Estrogen receptor α (ERα)-binding super-enhancers drive key mediators that control uterine estrogen responses in mice

2020 ◽  
Vol 295 (25) ◽  
pp. 8387-8400 ◽  
Author(s):  
Sylvia C. Hewitt ◽  
Sara A. Grimm ◽  
San-Pin Wu ◽  
Francesco J. DeMayo ◽  
Kenneth S. Korach
Keyword(s):  
Estrogen Receptor ◽  
Hormonal Regulation ◽  
Transforming Growth Factor ◽  
Retinoic Acid Receptor ◽  
Estrogen Receptor Α ◽  
Uterine Tissue ◽  
Chromosome Conformation ◽  
Estrogen Exposure

Estrogen receptor α (ERα) modulates gene expression by interacting with chromatin regions that are frequently distal from the promoters of estrogen-regulated genes. Active chromatin-enriched “super-enhancer” (SE) regions, mainly observed in in vitro culture systems, often control production of key cell type–determining transcription factors. Here, we defined super-enhancers that bind to ERα in vivo within hormone-responsive uterine tissue in mice. We found that SEs are already formed prior to estrogen exposure at the onset of puberty. The genes at SEs encoded critical developmental factors, including retinoic acid receptor α (RARA) and homeobox D (HOXD). Using high-throughput chromosome conformation capture (Hi-C) along with DNA sequence analysis, we demonstrate that most SEs are located at a chromatin loop end and that most uterine genes in loop ends associated with these SEs are regulated by estrogen. Although the SEs were formed before puberty, SE-associated genes acquired optimal ERα-dependent expression after reproductive maturity, indicating that pubertal processes that occur after SE assembly and ERα binding are needed for gene responses. Genes associated with these SEs affected key estrogen-mediated uterine functions, including transforming growth factor β (TGFβ) and LIF interleukin-6 family cytokine (LIF) signaling pathways. To the best of our knowledge, this is the first identification of SE interactions that underlie hormonal regulation of genes in uterine tissue and optimal development of estrogen responses in this tissue.

Sign in / Sign up

Export Citation Format

Share Document