Synthesis of 1,3,4-oxadiazoles as promising anticoagulant agents

RSC Advances ◽  
2016 ◽  
Vol 6 (29) ◽  
pp. 24797-24807 ◽  
Author(s):  
Vishwanathan B. Iyer ◽  
Gurupadayya B. M. ◽  
Bharathkumar Inturi ◽  
Venkata Sairam K. ◽  
Gurubasavaraj V. Pujar
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Vitamin K ◽  
Factor Xa ◽  
Docking Simulation ◽  
Molecular Docking Simulation ◽  
Vitamin K Epoxide Reductase ◽  
Target Proteins ◽  
Anticoagulant Agents ◽  
Epoxide Reductase

A series of 1,3,4-oxadiazoles were designed and subjected to molecular docking simulation onto the enzymes vitamin K epoxide reductase (PDB: 3KP9) and factor Xa (PDB: 1NFY) to visualize their binding affinity towards the said target proteins.

scholarly journals in silico Anti-Cholinestarase Activity of Flavonoids: A Computational Approach

2019 ◽  
Vol 31 (12) ◽  
pp. 2859-2864
Author(s):  
Niraj Kumar Singh ◽  
Somdutt Mujwar ◽  
Debapriya Garabadu
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Computational Approach ◽  
Molecular Docking Simulation ◽  
Flavonoid Compounds ◽  
Potent Inhibition ◽  
Potential Binding ◽  
Derivatives Of

In the present study, a computational approach has been designed to evaluate the potential anti-cholinesterase activity of derivatives of flavonoids. Molecular docking studies is performed for the 9 flavonoids against the human acetylcholine (ACh) enzyme to evaluate their binding affinity for having anti-alzheimer activity. All the 9 flavonoid compounds exhibited strong binding affinity that promises potent inhibition of human acetylcholine enzyme. Potential binding affinity of all the flavonoids against human acetylcholine enzyme confirms their possible mechanism of action by using AutoDock based molecular docking simulation technique. Thus, these flavonoid compounds could be presumed to be potential anti-cholinesterase drugs.

scholarly journals Homology modeling and molecular docking simulation of some novel imidazo[1,2-a]pyridine-3-carboxamide (IPA) series as inhibitors of Mycobacterium tuberculosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mustapha Abdullahi ◽  
Shola Elijah Adeniji ◽  
David Ebuka Arthur ◽  
Abdurrashid Haruna
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Docking ◽  
Homology Modeling ◽  
Binding Affinity ◽  
Docking Simulation ◽  
Computational Method ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Standard Drug ◽  
Molecular Docking Simulation

Abstract Background Tuberculosis (TB) remains a serious global health challenge that is caused by Mycobacterium tuberculosis and has killed numerous people. This necessitated the urgent need for the hunt and development of more potent drugs against the fast-emerging extensively drug-resistant (XDR) and multiple-drug-resistant (MDR) M. tuberculosis strains. Mycobacterium tuberculosis cytochrome b subunit of the cytochrome bc1 complex (QcrB) was recognized as a potential drug target in M. tuberculosis (25618/H37Rv) for imidazo[1,2-a]pyridine-3-carboxamides whose crystal strucuture is not yet reported in the Protein Data Bank (PDB). The concept of homology modeling as a powerful and useful computational method can be applied, since the M. tuberculosis QcrB protein sequence data are available. Results The homology model of QcrB protein in M. tuberculosis was built from the X-ray structure of QcrB in M. smegmatis as a template using the Swiss-Model online workspace. The modeled protein was assessed, validated, and prepared for the molecular docking simulation of 35 ligands of N-(2-phenoxy)ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA) to analyze their theoretical binding affinities and modes. The docking results showed that the binding affinity values ranged from − 6.5 to − 10.1 kcal/mol which confirms their resilience potency when compared with 6.0kcal/mol of isoniazid standard drug. However, ligands 2, 7, 22, 26, and 35 scored higher binding affinity values of − 9.60, − 9.80, − 10.10, − 10.00, and − 10.00 kcal/mol, and are respectively considered as the best ligands among others with better binding modes in the active site of the modeled QcrB protein. Conclusion The information derived in this research revealed some potential hits and paved a route for structure-based drug discovery of new hypothetical imidazo pyridine amide analogs as anti-tubercular drug candidates.

scholarly journals Unveiling novel inhibitors of dopamine transporter via in silico drug design, molecular docking, and bioavailability predictions as potential antischizophrenic agents

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabitu Babatunde Olasupo ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Binding Affinity ◽  
Dopamine Transporter ◽  
Hydrophobic Interactions ◽  
Docking Simulation ◽  
Experimental Investigations ◽  
Template Molecule ◽  
Molecular Docking Simulation ◽  
Drug Candidates

Abstract Background The inhibition of dopamine transporter is known to play a significant role in the treatment of schizophrenia-related and other mental disorders. In a continuing from our previous study, computational drug design approach, molecular docking simulation, and pharmacokinetics study were explored for the identification of novel inhibitors dopamine transporter as potential Antischizophrenic agents. Consequently, thirteen (13) new inhibitors of dopamine transporter were designed by selecting the molecule with serial number 39 from our previous study as the template molecule because  it exhibits good pharmacological attributes. Results Molecular docking simulation results revealed excellent molecular interactions between the protein target (PDB: 4m48) and the ligands (designed inhibitors) with major interactions that involved hydrogen bonding and hydrophobic interactions. Also, some of the designed inhibitors displayed a superior binding affinity range from − 10.0 to − 10.7 kcal/mol compared to the referenced drug (Lumateperone) with a binding affinity of − 9.7 kcal/mol. Computed physicochemical parameters showed that none of the designed inhibitors including the referenced drug violate Lipinski’s rule of five indicating that all the designed inhibitors would be orally bioavailable as potential drug candidates. Similarly, the ADMET/pharmacokinetics evaluations of some designed inhibitors revealed that they possessed good absorption, distribution, metabolism and excretion properties and none of the inhibitors is neither carcinogens nor toxic toward human ether-a-go-go related gene (hERG I) inhibitor or skin sensitization. Likewise, the BOILED-Egg graphics unveils that all the designed inhibitors demonstrate a high probability to be absorbed by the human gastrointestinal tract and could permeate into the brain. Besides, the predicted bioactive parameters suggested that all the selected inhibitors would be active as drug candidates. Furthermore, the synthetic accessibility scores for all the selected inhibitors and referenced drug lied within the easy zone (i.e., between 1–4) with their computed values range from 2.55 to 3.92, this implies that all the selected inhibitors would be very easy to synthesize in the laboratory. Conclusions Hence, all the designed inhibitors having shown excellent pharmacokinetics properties and good bioavailabilities attributes with remarkable biochemical interactions could be developed and optimized as novel Antischizophrenic agents after the conclusion of other experimental investigations.

Comparison of vitamin K1 and K2 kinetics of vitamin K epoxide reductase C1

2008 ◽  
Vol 28 (S 01) ◽  
pp. S106-S106
Author(s):  
P. Westhofen ◽  
M. Watzka ◽  
M. Hass ◽  
C. Müller-Reible ◽  
D. Lütjohann ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K1 ◽  
Vitamin K Epoxide Reductase ◽  
Epoxide Reductase ◽  
Kinetics Of

Vitamin K epoxide reductase significantly improves carboxylation in a cell line overexpressing factor X

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3811-3815 ◽  
Author(s):  
Yan-Mei Sun ◽  
Da-Yun Jin ◽  
Rodney M. Camire ◽  
Darrel W. Stafford
Keyword(s):  
Binding Site ◽  
Cell Line ◽  
Vitamin K ◽  
Turnover Rate ◽  
Factor X ◽  
Vitamin K Epoxide Reductase ◽  
Transfected Cells ◽  
Epoxide Reductase ◽  
A Cell ◽  
Practical Implications

Previously we reported that we could increase the fraction of carboxylated factor X by reducing the affinity of the propeptide for its binding site on human gamma glutamyl carboxylase. We attributed this to an increased turnover rate. However, even with the reduced affinity propeptide, when sufficient overproduction of factor X is achieved, there is still a significant fraction of uncarboxylated recombinant factor X. We report here that the factor X of such a cell line was only 52% carboxylated but that the fraction of carboxylated factor X could be increased to 92% by coexpressing the recently identified gene for vitamin K epoxide reductase. Because vitamin K is in excess in both the untransfected and vitamin K epoxide reductase (VKOR)–transfected cells, the simplest explanation for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone. In addition to its mechanistic relevance, this observation has practical implications for overproducing recombinant vitamin K–dependent proteins for therapeutic use.

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