Active-site studies of neurohypophyseal hormones: synthesis and pharmacological properties of [5-(N4,N4-dimethylasparagine)]oxytocin

1979 ◽  
Vol 22 (7) ◽  
pp. 890-893 ◽  
Author(s):  
Roderich Walter ◽  
Glenn L. Stahl ◽  
Themistoeles Caplaneris ◽  
Paul Cordopatis ◽  
Dimitrios Theodoropoulos
Keyword(s):  
Active Site ◽  
Pharmacological Properties ◽  
Neurohypophyseal Hormones

scholarly journals Targeting SARS-CoV-2 nonstructural protein 15 endoribonuclease: an in silico perspective

2021 ◽  
Author(s):  
Shafi Mahmud ◽  
Abdo A Elfiky ◽  
Al Amin ◽  
Sumon Chandro Mohanto ◽  
Ekhtiar Rahman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
In Silico ◽  
Nonstructural Protein ◽  
Pharmacological Properties ◽  
Binding Pattern ◽  
Human Coronavirus ◽  
Nonbonded Interactions ◽  
Active Site Cavity ◽  
Approved Drugs

The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15 (Nsp15). We screened 23 drugs, from which three (saquinavir, valrubicin and aprepitant) show a paramount predicted binding affinity (-9.1, -9.6 and -9.2 kcal/mol, respectively) against SARS-CoV-2 Nsp15. Moreover, saquinavir and aprepitant make nonbonded interactions with Leu201 in the active site cavity of Nsp15, while the drug valrubicin interacts with Arg199 and Leu201. This binding pattern may be effective against the targeted protein, leading to Nsp15 blockage and virus abolition. Additionally, the pharmacological properties of the screened drugs are known since they have been approved against different viruses.

Active site studies of neurohypophyseal hormones. Comparison of oxytocin and arginine vasopressin analogs containing 2-D-tyrosine

1979 ◽  
Vol 101 (10) ◽  
pp. 2717-2721 ◽  
Author(s):  
Victor J. Hruby ◽  
Donald A. Upson ◽  
Diane M. Yamamoto ◽  
Clark W. Smith ◽  
Roderich Walter
Keyword(s):  
Arginine Vasopressin ◽  
Active Site ◽  
Neurohypophyseal Hormones

scholarly journals Solution structure of conformationally restricted vasopressin analogues.

2004 ◽  
Vol 51 (1) ◽  
pp. 33-49 ◽  
Author(s):  
Emilia Trzepałka ◽  
Marta Oleszczuk ◽  
Maciej Maciejczyk ◽  
Bernard Lammek
Keyword(s):  
Aqueous Solution ◽  
Solution Structure ◽  
Pharmacological Properties ◽  
Spatial Structures ◽  
Conformationally Restricted ◽  
Nmr Data ◽  
Neurohypophyseal Hormones ◽  
Selective Antagonists ◽  
Vasopressin Analogues ◽  
Method Show

In recent years, a massive effort has been directed towards designing potent and selective antagonists of neurohypophyseal hormones substituted at position 3. Modification of vasopressin at position 3 with 4,4'-biphenylalanine results in pharmacologically inactive analogues. Chemically, this substitution appears to vary only slightly from those previously made by us (1-Nal or 2-Nal), which afforded potent agonists of V(2) receptors. In this situation, it seemed worthwhile to study the structure of the analogues with 4,4'-biphenylalanine (BPhe) at position 3 in aqueous solution using NMR spectroscopy and total conformational analysis. This contribution is part of extensive studies aimed at understanding spatial structures of 3-substituted [Arg(8)]vasopressin analogues of different pharmacological properties. NMR data were used to calculate 3D structures for all the analogues using two methods, EDMC with the ECEPP/3 force field, and molecular dynamic with the simulated annealing (SA) algorithm. The structures obtained by the first method show a better fit between the NMR spectral evidence and the calculation for all the peptides.

scholarly journals Traditional Phytochemistry: Identification of Drug by ‘Taste’

2007 ◽  
Vol 4 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Kalpana Joshi ◽  
Alex Hankey ◽  
Bhushan Patwardhan
Keyword(s):  
Traditional Medicine ◽  
Active Site ◽  
Active Sites ◽  
The Body ◽  
Pharmacological Properties ◽  
Specific Enzyme ◽  
Materia Medica ◽  
Enzyme Active Site ◽  
Scientific Approach ◽  
Hypo Thesis

Ayurveda, the system of traditional medicine from India, holds that ‘Rasa’, a concept roughly corresponding to taste, is a basis for identifying pharmacological properties of plants and other materia medica used in Dravyaguna—its system of phytomedicine. This idea has recently found support in studies of ibuprofen, the pharmacological properties of which are similar to those of oleocanthal, because the two substances have very similar tastes. This paper discusses a possible scientific approach to understanding the Ayurvedic (hypo)thesis in terms of the stereochemical basis of both pharamaco-activity and taste, and the numbers of possible pharmaco-active compounds that ‘Rasa’ may be able to distinguish. We conclude that molecules binding to a specific enzyme active site should have their own ‘Rasa’, and that the number of different subjectively experienced ‘tastes’ is more than enough to distinguish between molecular shapes binding to all enzyme active sites in the body.

Synthesis of cyclohexylaliphatic acids and their pharmacological properties

1986 ◽  
Vol 51 (12) ◽  
pp. 2896-2908 ◽  
Author(s):  
Miroslav Kuchař ◽  
Bohumila Brunová ◽  
Jaroslava Grimová ◽  
Stanislav Vaněček ◽  
Jiří Holubek
Keyword(s):  
Double Bond ◽  
Experimental Model ◽  
Active Site ◽  
Wittig Reaction ◽  
Qualitative Assessment ◽  
Pharmacological Properties ◽  
Phenyl Derivative ◽  
Anti Inflammatory ◽  
Fibrinolytic Capacity ◽  
Inflammatory Effect

A series of substituted cyclohexylacetic acids I has been obtained by hydrogenation of the unsaturated analogues II and III. Esters of these analogues were prepared by the Horner-Wittig reaction of the corresponding cyclohexanones IV and/or 2-cyclohexenones V with triethyl phosphonoacetate. These esters were obtained in two isomeric forms (Z and E), differing in the double bond in the exo-position. The derivatives with a substituent in the 2-position exhibited a partial shift of the double bond to the cyclohexane ring; this shift was especially marked in the 2-phenyl derivative. With the acids I-III, activation of fibrinolysis was assessed by the hanging clot method; the anti-inflammatory effect was assessed by inhibition of two experimental model inflammations. The regression equation relating fibrinolytic capacity to lipophilicity was a quadratic one, the logarithm of optimum lipophilicity being log Popt = 5.55. A qualitative assessment of the anti-inflammatory effect in relation to lipophilicity suggests that log Popt is probably higher than with arylaliphatic acids. These acids seem to have an active site different from that of the acids I-III.

In Silico Based Approach to Investigate Plant Lignans as inhibitor Candidates for Estrogen Receptor in Breast Cancer

2021 ◽  
Vol 08 ◽  
Author(s):  
Farzaneh Mohamadyar-Toupkanlou ◽  
Mina Esfandiari ◽  
Mahshid Sadat Kashef-Saberi ◽  
Mahboubeh Kabiri ◽  
Zahra Bazi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Estrogen Receptor Alpha ◽  
Inhibitory Effect ◽  
Pharmacological Properties ◽  
Active Site Pocket ◽  
Plant Lignans

Background: In the last decades, growing evidence demonstrates interest in phytoestrogen intake to modulate targets in different types of cancer. Plant lignans have proven efficacious in blocking estrogen receptors of breast cancer cells. Among them, four phytoestrogen lignans: pinoresinol, matairesinol, lariciresinol, and secoisolariciresinol have been most studied. However, available studies have mostly dealt with anti-cancer effects of groups of lignans in certain foods or plants and the effects of specific lignans, especially from a molecular interaction viewpoint, have been rarely addressed in the literature. Objective: We aimed to in silico predict pharmacological properties, binding ability and binding strength of pinoresinol, matairesinol, lariciresinol and secoisolariciresinol as possible inhibitors of estrogen receptor alpha which is the most important biomarker in breast cancer. Methods: Firstly, we evaluated the pharmacological properties of four lignans using SwissADME. Then we investigated the ligand-receptor interactions of these molecules as positively appraised ligands for ER-positive breast cancer targeted therapy using docking method. We finally compared the inhibitory effect possibility of the lignans against endoxifen which is the active metabolite of tamoxifen. Results: The best binding affinity of endoxifen, matairesinol, pinoresinol, lariciresinol and secoisolariciresinol were respectively -9.2, -7.5, -6.7, -6.7, -5.8 kcal/mol. In the meantime, matairesinol showed the minimum binding energy than other studied lignans in addition to the most similar interactions to endoxifen with conserved domain residues of the active site pocket in Leu:391, Ala:350, Met:421, and Phe:404. Conclusion: Among the studied lignans, matairesinol showed the favorable pharmacokinetics and drug-likeliness properties, the least binding energy as well as the most common interactions in conserved residues of the active site pocket with estrogens. This makes it a molecule with low number of nonspecific interactions, better target selectivity, and hence fewer side effects. Thus, our results introduce matairesinol as a possibly effective anti-estrogen receptor inhibitor candidate.

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