scholarly journals Vibrational Spectroscopic and Molecular Docking Studies of Amrinone, a Cardiotonic Inotropic Drug-=SUP=-*-=/SUP=-

2022 ◽  
Vol 130 (2) ◽  
pp. 236
Author(s):  
Sefa Celik ◽  
Sevim Akyuz ◽  
Aysen E. Ozel ◽  
Elif Akalin
Keyword(s):  
Molecular Docking ◽  
Vibrational Spectra ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Docking Studies ◽  
Stable Conformation ◽  
Docking Simulations ◽  
Phosphodiesterase 3 ◽  
Title Molecule ◽  
Delta G

Amrinone is a class I cardiotonic inotropic agent, which is known to increase the cyclic adenosine monophosphate (cAMP) level by inhibiting the phosphodiesterase 3 (PDE3) enzyme. In this study the theoretically possible stable conformations of the amrinone, was examined first by conformational analysis method and then the obtained most stable conformation was optimized by DFT/wb97xd/6-311++G(d,p) level of theory using Gaussian 03 program. The credibility of the theoretical model was confirmed by comparison of experimental and theoretical vibrational spectra of the title molecule. The fundamental vibrational wavenumbers, IR and Raman intensities of the optimized structure of amrinone were determined using DFT/wb97xd/6-311++G(d,p) level of theory and compared with the experimental vibrational spectra. To investigate the influence of amrinone on cAMP enhancement, the docking simulations towards PDE3B were carried out and the main binding interactions of amrinone with PDE3 were elucidated. Cytochrome P450s (CYPs) are very important phase I metabolizing enzymes. The interaction between amrinone and CYPs (CYP1A2, CYP2C9 and CYP2C19) was investigated by docking simulations. Moreover, molecular docking of the title molecule with different proteins and receptors were studied to reveal potential mechanisms for therapeutic applications. Molecular docking simulations revealed that amrinone showed strong binding affinity to integrins α5β1 (Delta G=-6.6 kcal/mol) and αIIbβ3 (-6.6 kcal/mol), and DNA (-6.5 kcal/mol). The results correlated with its anticancer activity. The drug likeness and ADMET properties of amrinone were analyzed for the prediction of pharmacokinetic profiles. Key words: amrinone, DFT calculations, FTIR, Molecular Docking, ADMET.

scholarly journals Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4238
Author(s):  
Sergiy M. Kovalenko ◽  
Oleksandr G. Drushlyak ◽  
Svitlana V. Shishkina ◽  
Irina S. Konovalova ◽  
Illia O. Mariutsa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Combinatorial Libraries ◽  
Docking Studies ◽  
X Ray Diffraction ◽  
Docking Simulations ◽  
Design And Synthesis ◽  
Hbv Replication ◽  
Biological Studies ◽  
Reliable Design

Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CH3I has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CH3I led to the formation of both O- and N-methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of O-methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, 1H-NMR, 13C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate’s anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.

scholarly journals Synthesis, Spectral Characterization and Molecular Docking Studies of Novel Benzidin-bis-tetrahydroacridine Analogues

2020 ◽  
Vol 71 (5) ◽  
pp. 163-181
Author(s):  
Madalina Marina Hrubaru ◽  
Carmellina Daniela Badiceanu ◽  
Anthony Chinonso Ekennia ◽  
Sunday N. Okafor ◽  
Cristian Enache ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Modes ◽  
Docking Simulations ◽  
Ft Ir ◽  
Dynamics Simulations ◽  
And Behavior ◽  
Human Butyrylcholinesterase

Alzheimer�s is a progresive neurodegenerative disease that interferes with human cognitive ability, memory and behavior. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes are major therapeutic routes for the treatment of Alzheimer disease. In the study, nevel bis-polymethylenquinoline-bis-carboxamides (3a-f) and bis-polymethylenquinoline-bis-carboxylic acids (5a-b) having as precursor benzidine, were obtained in good yields by Pfitzinger condensation reactions of bis-isatines with corresponding cyclanones. The compounds were characterized by elemental analysis, FT-IR, NMR and mass spectrometry. Furthermore, the compounds were subjected to molecular docking dynamics simulations to ascertain their potentials as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Molecular docking simulations showed varied binding activities towards the two binding sites of acetylcholinesterase: 4EY7 and 1OCD, and human butyrylcholinesterase: 1P0I. Compounds 3e and 5b demostrated strong binding affinities with 1P0I, 1OCD and 4EY7 biotargets similar to the binding modes of donepezil and tacrine (co-crystallized inhibitors of acetylcholinesterase) and butyrate (co-crystallized inhibitors of butyrylcholinesterase).

Anti-Trypanosoma cruzi Activity and Molecular Docking Studies of 1Hpyrazolo[ 3, 4-b]pyridine Derivatives

2020 ◽  
Vol 17 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Camilo Henrique da Silva Lima ◽  
Júlio César de Araujo Vanelis Soares ◽  
Joana Lucius de Sousa Ribeiro ◽  
Estela Maris Freitas Muri ◽  
Sérgio de Albuquerque ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Phenyl Group ◽  
Docking Simulation ◽  
Docking Studies ◽  
Pyridine Derivatives ◽  
Trypanocidal Activity ◽  
Docking Simulations ◽  
Cytotoxicity Assays ◽  
Activity Screening ◽  
Insight Into

Background: Untargeted studies led to the development of some pyrazolopyridine derivatives for the antiparasitic profile, particularly the derivatives containing the structural carbohydrazide subunit. In this work, we proceeded in the biological screening of 27 N’- (substitutedphenylmethylene)- 4-carbohydrazide-3-methyl-1-phenyl-1H-pyrazolo[3, 4-b]pyridine derivatives against T. cruzi as well as the cytotoxic evaluation. To obtain more information about the trypanocidal activity of this class of compounds, we carried out molecular docking simulations to get an insight into putative targets in T. cruzi. Methods: The assays were evaluated against both trypomastigote and amastigote forms of T. cruzi and cytotoxicity assays on LLCMK2 cells. The predominant conformational compounds were analyzed and molecular docking simulations performed. Results: The results from trypanocidal activity screening of this series showed that just the compounds with phenyl group at C-6 position exhibited activity and the N’-4-hydroxyphenylmethylene derivative presented the best profile against both trypomastigote and amastigote forms of T. cruzi. Docking simulation results showed that this compound has a binding affinity with both CYP51 and cruzain targets of T. cruzi. Conclusion: Our results indicate that the hydroxyl substituent at the N’-substituted-phenylmethylene moiety and the phenyl ring at C-6 of 1H-pyrazolo[3,4-b]pyridine system are relevant for the trypanocidal activity of this class of compounds. Also, docking simulations showed that activity presented can be related to more than one target of the parasite.

scholarly journals Molecular Simplification of Natural Products: Synthesis, Antibacterial Activity, and Molecular Docking Studies of Berberine Open Models

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 452
Author(s):  
Gualtiero Milani ◽  
Maria Maddalena Cavalluzzi ◽  
Roberta Solidoro ◽  
Lara Salvagno ◽  
Laura Quintieri ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Parent Compound ◽  
Biological Properties ◽  
Docking Studies ◽  
Bacterial Cell Division ◽  
Gram Positive ◽  
Test Species ◽  
Gram Negative ◽  
Docking Simulations

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target.

scholarly journals Synthesis, antimicrobial activity, urease inhibition and molecular docking studies of new proline linked thiourea derivatives

2020 ◽  
Vol 65 (9) ◽  
pp. 783-788
Author(s):  
Ahmad RAHEEL ◽  
◽  
Imtiaz-Ud DIN ◽  
Syed Hassan IFTIKHAR ◽  
Muhammad Babar TAJ ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Carboxylic Acids ◽  
Elemental Analysis ◽  
Binding Mode ◽  
Docking Studies ◽  
Urease Inhibition ◽  
Thiourea Derivatives ◽  
Molecular Docking Studies ◽  
Docking Simulations

A series of new thiourea based carboxylic acids (Ia-Ie) were synthesized and characterized by elemental analysis, FTIR and NMR (1 H and 13C) spectroscopy. They were preliminary bioassayed for their antibacterial, anifungal and urease inhibition activities. Molecular docking simulations were carried out to determine the probable binding mode of the synthesized compounds. The bioassay results showed that some of titled compounds exhibited encouraging results.

In Silico Prediction of P-glycoprotein Binding: Insights from Molecular Docking Studies

2019 ◽  
Vol 26 (10) ◽  
pp. 1746-1760 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sánchez ◽  
Eugenio Uriarte
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Studies ◽  
Efflux Transporter ◽  
Molecular Docking Studies ◽  
Docking Simulations ◽  
Central Nervous System Drugs ◽  
P Glycoprotein ◽  
Molecular Mechanism Of Action ◽  
Key Residues

The P-glycoprotein is an efflux transporter that expels substances out of the cells and has an important impact on the pharmacokinetic and pharmacodynamic properties of drugs. The study of the interactions between ligands and the P-glycoprotein has implications in the design of Central Nervous System drugs and their transport across the blood-brain barrier. Moreover, since the P-glycoprotein is overexpressed in some types of cancers, the protein is responsible for expelling the drug therapies from the cells, and hence, for drug resistance. In this review, we describe different P-glycoprotein binding sites reported for substrates, inhibitors and modulators, and focus on molecular docking studies that provide useful information about drugs and P-glycoprotein interactions. Docking in crystallized structures and homology models showed potential in the detection of the binding site and key residues responsible for ligand recognition. Moreover, virtual screening through molecular docking discriminates P-glycoprotein ligands from decoys. We also discuss challenges and limitations of molecular docking simulations applied to this particular protein. Computational structure-based approaches are very helpful in the study of novel ligands that interact with the P-glycoprotein and provide insights to understand the P-glycoprotein molecular mechanism of action.

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