scholarly journals Method of molecular docking in the design of new progesterone analogues

2020 ◽  
Vol 17 (4) ◽  
pp. 65-74
Author(s):  
Mariya A. Petrosyan ◽  
Daria A. Belinskaia ◽  
Kseniia I. Taborskaia ◽  
Petr D. Shabanov
Keyword(s):  
Molecular Docking ◽  
Progesterone Receptor ◽  
Dissociation Constants ◽  
Amino Acid Residues ◽  
Ru 486 ◽  
Receptor Complexes ◽  
Human Progesterone Receptor ◽  
Related Compounds ◽  
Autodock 4.2 ◽  
Progesterone Analogues

The aim of this study is to carry out the molecular docking of gestagenic preparations and structurally related compounds to the isoform A of human progesterone receptor and to assess the applicability of this method for the active progestins search. Docking was done (using Autodock 4.2) of progesterone and 13 compounds with different gestagenic/antigestagenic activity (megestrol acetate; (3)-3-Hydroxy-6-methyl-20-oxopregna-4,6-dien-17-yl acetate (AMOL); Medroxyprogesterone-17-acetate; Levonorgestrel; Dydrogesterone; RU-486; Ulipristal acetate; (3)-17-Acetoxy-6-methyl-20-oxopregna-4,6-dien-3-yl butyrate; 16,17-Cyclohexanoprogesterone; 6-Methyl-16,17-cyclohexanoprogesterone; Proligestone; 16,17-Cyclopentanoprogesterone; 16,17-Cyclohex-3-enoprogesterone). Calculations of theoretical dissociation constants (Kd) of ligand-progesterone receptor complexes showed that it is possible to evaluate the probability of activity of a candidate compound using the Autodock 4.2 program, but it requires caution, taking into account the lack of the link between Kd and gestagen activity. In addition, the method allows to identify compounds that change the position of amino acid residues in the ligand-binding domain of PR-A after binding (that is possibly have a different mechanism of action), as well as substances that do not interact with the agonistic form of the receptor due to other causes.

ALTERATIONS IN PROGESTERONE RECEPTORS IN THE RAT UTERUS BEARING AN INTRA-UTERINE DEVICE DURING THE OESTROUS CYCLE AND EARLY PREGNANCY

1980 ◽  
Vol 87 (3) ◽  
pp. 365-373 ◽  
Author(s):  
LESLIE MYATT ◽  
M. G. ELDER ◽  
LOUIS LIM
Keyword(s):  
Progesterone Receptor ◽  
Nuclear Receptor ◽  
Early Pregnancy ◽  
Dissociation Constants ◽  
Progesterone Receptors ◽  
Oestrous Cycle ◽  
Rat Uterus ◽  
Binding Characteristics ◽  
Receptor Complexes ◽  
And Control

The binding characteristics, content and intracellular distribution of cytosolic and nuclear progesterone receptors have been investigated, using [3H]progesterone as ligand, in the rat uterus bearing a unilateral intra-uterine device (IUD) during the oestrous cycle and from days 3 to 6 of pregnancy. The dissociation constants of nuclear and cytosolic progesterone–receptor complexes for IUD-containing and control uterine horns were similar. Cytosolic receptor concentrations in the IUD-containing uterus were always lower but changed in a manner similar to the control during the periods studied. Nuclear receptor concentrations in the control horn reflected changes in hormone levels during the oestrous cycle although concentrations measured were greater than previously reported. However, in IUD-containing uteri the pattern was completely reversed with minimal levels at pro-oestrus. Nuclear receptor concentrations were little different in both horns during early pregnancy. Total progesterone receptor synthesis determined between metoestrus and pro-oestrus in IUD-containing horns was significantly less than that of control horns. This correlated with the attenuated rise of nuclear oestrogen receptor levels previously observed between these times in IUD-containing uterine horns.

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

scholarly journals Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

1997 ◽  
Vol 11 (8) ◽  
pp. 1114-1128 ◽  
Author(s):  
Marc J. Tetel ◽  
Soryung Jung ◽  
Patricia Carbajo ◽  
Teri Ladtkow ◽  
Debra F. Skafar ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Amino Terminal ◽  
Human Progesterone Receptor
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