inhibition constant
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2021 ◽  
pp. 028-032
Author(s):  
Sharma Shaweta ◽  
Sharma Akhil ◽  
Gupta Utsav

Background: The COVID-19 pandemic is a major concern. However, its association and rising cases of mucormycosis, also known as black fungus make the scenario even more troublesome. In addition, no specific medication against mucormycosis/black fungus makes things even worse. Objective: Garlic phytoconstituents have shown remarkable antifungal properties against various fungal species in various studies. Thus, the objective of the study was to check the potency of garlic phytoconstituents against the 1,3-beta-glucan synthase fungal protein using in-silico methods. Method: Auto Dock was used to evaluate selected garlic phytochemical molecules against 1,3-beta-glucan synthase fungal protein, and Discovery studio visualizer was used to create 3D and 2D interaction photos. Results: Five out of 9 phytoconstituents were found to form conventional hydrogen bonds, and only alliin formed the highest number of hydrogen bonds. However, the binding energy and inhibition constant of all nine phytoconstituents were determined. Interestingly, Z-ajoene showed the lowest binding energy of -5.07 kcal/mol and inhibition constant of 192.57µM. Conclusion: The results of our investigation suggested that garlic phytochemicals can have a good impact against black fungi, pertaining to the significant binding energies of phytoconstituents during blind docking. Specifically, Z-ajoene could be a good alternate against black fungi. However, detailed research is required to explore the antifungal activity of garlic against mucormycosis.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5957
Author(s):  
Syed Amir Ashraf ◽  
Abd Elmoneim O. Elkhalifa ◽  
Khalid Mehmood ◽  
Mohd Adnan ◽  
Mushtaq Ahmad Khan ◽  
...  

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.


2021 ◽  
Author(s):  
Shaweta Sharma ◽  
Akhil Sharma ◽  
Utsav Gupta

Abstract Background: The COVID-19 pandemic is a major concern. However, its association and rising cases of mucormycosis, also known as black fungus make the scenario even more troublesome. In addition, no specific medication against mucormycosis/black fungus makes things even worse.Objective: Garlic phytoconstituents have shown remarkable antifungal properties against various fungal species in various studies. Thus, the objective of the study was to check the potency of garlic phytoconstituents against the 1,3-beta-glucan synthase fungal protein using in-silico methods.Method: Auto Dock was used to evaluate selected garlic phytochemical molecules against 1,3-beta-glucan synthase fungal protein, and Discovery studio visualizer was used to create 3D and 2D interaction photos.Results: Five out of 9 phytoconstituents were found to form conventional hydrogen bonds, and only alliin formed the highest number of hydrogen bonds. However, the binding energy and inhibition constant of all nine phytoconstituents were determined. Interestingly, Z-ajoene showed the lowest binding energy of -5.07 kcal/mol and inhibition constant of 192.57µM.Conclusion: The results of our investigation suggested that garlic phytochemicals can have a good impact against black fungi, pertaining to the significant binding energies of phytoconstituents during blind docking. Specifically, Z-ajoene could be a good alternate against black fungi. However, detailed research is required to explore the antifungal activity of garlic against mucormycosis.


Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1663
Author(s):  
Yen-Hui Lin

The biodegradation kinetics of 4-chlorophenol (4-CP) and phenol and microbial growth of Pseudomonas putida (P. putida) cells were estimated in batch and biofilm reactors. The kinetic parameters of cells on phenol were determined using the Haldane formula. The maximum specific growth rate of P. putida on phenol, the half-saturation constant of phenol and the self-inhibition constant of phenol were 0.512 h−1, 78.38 mg/L and 228.5 mg/L, respectively. The yield growth of cells on phenol (YP) was 0.618 mg phenol/mg cell. The batch experimental results for the specific transformation rate of 4-CP by resting P. putida cells were fitted with Haldane kinetics to evaluate the maximum specific utilization rate of 4-CP, half-saturation constant of 4-CP, and self-inhibition constant of 4-CP, which were 0.246 h−1, 1.048 mg/L and 53.40 mg/L, respectively. The negative specific growth rates of cells on 4-CP obtained were fitted using a kinetic equation to investigate the true transformation capacity and first-order endogenous decay coefficient, which were 4.34 mg 4-CP/mg cell and 5.99 × 10−3 h−1, respectively. The competitive inhibition coefficients of phenol to 4-CP transformation and 4-CP to phenol degradation were 6.75 and 9.27 mg/L, respectively; therefore, phenol had a higher competitive inhibition of 4-CP transformation than the converse. The predicted model examining cometabolic transformation of 4-CP and phenol degradation showed good agreement with the experimental observations. The removal efficiencies for phenol and 4-CP were 94.56–98.45% and 96.09–98.85%, respectively, for steady-state performance.


2021 ◽  
Vol 9 (2) ◽  
pp. 114-129
Author(s):  
E. A. Jain (Korsakova) ◽  
D. V. Demchenko ◽  
A. A. Ozerov ◽  
M. N. Makarova ◽  
V. G. Makarov ◽  
...  

The aim of the study is to identify 1-[2-(2-benzoylphenoxy) ethyl]-6-methyluracil using various methods of analysis, as well as to study its action mechanism against wild-type and mutant forms of HIV-1 reverse transcriptase (RT).Materials and methods. To characterize the structure of the test substance, a few kinds of analysis (X-ray diffraction, elemental, thermal) as well as a few kinds of spectroscopy (UV, IR, and NMR) have been used. The study of the action mechanism of the compound as a potential drug was carried out by evaluating the inhibitory activity against HIV-1 RT wild-type and its mutant forms corresponding to drug-resistant viral strains.Results. The studies have been carried out to confirm the structure of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil. The UV spectrum has a pronounced absorption maximum when measuring a solution of the substance in tetrahydrofuran at the concentration of 0.10 mg / ml. In the IR spectrum, there are specific bands in the range of 4000-370 cm–1. These factors make it possible to use UV and IR spectra to identify the test compound in the substance. It has also been established that the number and mutual arrangement of functional groups, the integrated intensity of signals in the 1H-NMR spectrum, as well as the structure of the carbon skeleton, correspond to the structure of 1-[2-(2-benzoylphenoxy) ethyl]-6-methyluracil. The results of studying the action mechanism showed that the test compound is an effective inhibitor of wild-type HIV-1 RT with an inhibition constant of 0.2 µM, as well as an enzyme inhibitor (mutation G190A) with an inhibition constant of 8 µM; enzyme (mutation Y181C) with an inhibition constant of 10 µM, as well as a reverse transcriptase (RT) inhibitor (mutation L100I, K103N, V106A) and a double mutant K103N / Y181C with an inhibition constant of more than 20 µM.Conclusion. As a result of the performed X-ray structural, elemental, 1H-NMR and 13C-NMR analyzes, the structure of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil has been confirmed. The possibility of using UV, IR and NMR spectroscopy, as well as thermal analyzes to confirm the authenticity during the verification of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, has been shown. The developed methods can be used in the quality control and included in the draft of practice guidelines for the investigated substance. The studies of the action mechanism of the compound of HIV-1 RT reverse transcriptase have shown that this compound belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1.


2021 ◽  
Author(s):  
IVAN VITO FERRARI ◽  
Paolo Patrizio

Background: HAS (Human Serum Albumin) is a highly water-soluble globular plasma protein, with a relative molecular weight (g/mol) of 67 KDa, consisting of 585 amino acid residues. In this study, we have investigated the interaction of the crystal structures complexed in human serum albumin at resolutions of 2.8 to 2.0: Camptothecin, 9-amino-camptothecin, Etoposide, Teniposide, Bicalutamide and Idarubicin, using a bioinformatic approach, estimated by Pyrx Virtual Screen Tool and AMDock ( AMDock, Assisted Molecular Docking). We have analyzed a validated protocol, studying several parameters, as Binding Affinity, RMSD value, Ligand Efficiency, and Inhibition constant (Ki value). Methods: Human Serum Albumin protein preparation was characterized with several programs, as Chimera, MGLTools 1.5.6, Swiss PDB Viewer Software to perform docking analysis by Autodock Vina estimated with Pyrx Software. Results: In this work, we found crystalized camptothecin, 9-amino-camptothecin and teniposide, gave excellent results for Binding Affinity, (kcal/mol), RMSD value (A ), inhibition constant Ki value (nM): -Binding Affinity of 9-amino-camptothecin (ca.-10 kcal/mol), camptothecin ( -9 kcal/mol) and teniposide ( -11 kcal/mol, -RMSD Value of 9 -amino-camptothecin (ca.1.8 A ), camptothecin (ca.2.2 A ) and teniposide (ca. 3.6 A), - Ki Value: 9 -amino-camptothecin (ca 59 nM), camptothecin ( ca 183 nM) and teniposide ( ca 9 nM), -Ligand efficiency: of 9 -amino-camptothecin(ca -0.35 kcal/mol) , camptothecin (ca -0.34 kcal/mol) and teniposide (ca -0.24 kcal/mol Conclusions: We explored the best three crystallized ligand in Human Serum Albumin. Moreover, we have observed a complete overlap, during the re-docking analysis phase, estimated by chimera Software. Therefore we have concluded that ID PDB Crystal 4L8U human serum albumin-Crystallised 9 -amino Camptothecin; ID PDB Crystal 4L9K human serum albumin- Crystallised Camptothecin and ID PDB Crystal 4L9Q human serum albumin-Crystallised teniposide be used as a possible as a reference template protein to be compared with the target protein, by Docking molecular analysis.


Author(s):  
Naseer Maliyakkal ◽  
Ipek Baysal ◽  
Anandkumar Tengli ◽  
Gulberk Ucar ◽  
Mohammad Ali Abdullah Almoyad ◽  
...  

Background: Chalcones with methoxy substituents are considered as a promising framework for the inhibition of monoamine oxidase (MAO) enzymes. Methods: A series of nine trimethoxy substituted chalcones (TMa-TMi) was synthesized and evaluated as a multifunctional class of MAO inhibitors. All the synthesized compounds were investigated for their in vitro MAO inhibition, kinetics, reversibility, blood-brain barrier (BBB) permeation, and cytotoxicity and antioxidant potentials. Results: In the present study, compound (2E)-3-(4-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (TMf) was provided with an MAO-A inhibition constant value equal to 3.47±0.09 μM and with a selectivity of 0.008. Thus, it was comparable to that of moclobemide, a well known potent hMAO-A inhibitor (SI=0.010). Compound (2E)-3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (TMh) showed good MAO-B inhibition, with an inhibition constant of 0.46±0.009 μM. The PAMPA assay demonstrated that all the synthesized derivatives can cross the BBB successfully. The cytotoxicity studies revealed that TMf and TMh have 88.22 and 80.18 % cell viability at 25 µM. Compound TMf appeared as the most promising antioxidant molecule with IC50 values, relative to DPPH and H2O2 radical activities, equal to 6.02±0.17 and 7.25±0.07 μM. To shed light on the molecular interactions of TMf and TMh towards MAO-A and MAO-B, molecular docking simulations and MM/GBSA calculations have been carried out. Conclusion: The lead molecules TMf and TMh with multi-functional nature can be further employed for the treatment of various neurodegenerative disorders and depressive states.


2021 ◽  
Vol 46 (2) ◽  
Author(s):  
O. O. Adeboye ◽  
S. A. Agboluaje ◽  
O. F. Akinyele

The use of synthetic drugs is associated with various side effects and it is important to look for other drugs from medicinal plants. Therefore, this study aimed at assessing the inhibitory activities of Calotropis procera leaf against α-glucosidase hydrolase Sus B and it‟s possible mode of inhibiting this enzyme through molecular docking studies. From the molecular docking analysis, the results shows that out of the thirty six (36) screened phytochemicals, only twenty six (26) fall between the recommended hit value of inhibition constant of (0.1-1.0 µM) where their inhibition constant range from (0.01-0.59 µM) after docking with target receptor α-glucosidase hydrolase SusB (PDB ID: 2ZQ0) using Pyrx-vitual screening tools (Autodock tool, Autodock vina and Open babel).Visualizing was done using Pymol and Biosvia discovery studio(2019). Considering the other analysis done, Drug likeness of Lipinski rule of five, only six(6): Hesperidine (3),Calotroposide (3),Calotropin (3),Ascleposide (4),Proceroside (4) and Voruschairin (3) out of the potent twenty six (26) contravene more than 2 of the Lipinski rules of five, therefore other twenty (20) compounds can be considered for processing into potent drugs.


Author(s):  
Khalid Alshaghdali

In young children, immunocompromised individuals, and elderly people, the respiratory syncytial virus (RSV) is the primary source of acute lower respiratory tract infection. Intervention with RSV-specific small-molecule antivirals may provide significant therapeutic potential. For virus entry, the RSV fusion protein (F) is crucial as it facilitates viral and hosts membrane fusion. To date, no approved vaccine or drug molecule is available to treat RSV. With this purpose, in the present study, virtual screening of a library of natural compounds against the active site of F protein was performed, followed by an in-depth molecular docking study of top-scored compounds. Selected hits ZINC8740013, ZINC4029781 and ZINC898642were found to strongly bind with RSV F protein relative to the other compounds as well as the control. The binding energy (BE) and inhibition constant for ‘ZINC8740013-RSV F’, ‘ZINC4029781-RSV F’, and ‘ZINC898642-RSVF’ complexes were found as ‘-7.8 kcal/mol and 63.27 µM’, ‘-7.7 kcal/mol and 19.04 µM’, and ‘-7.5 kcal/mol and 3.31 µM’, respectively. However, BE and inhibition constant of control (JNJ-53718678) with RSV F protein was found as -6.1 kcal/mol and 563.26 µM, respectively. Phe140 and Phe488 are the main interacting residues of RSV F protein with JNJ-53718678 and selected hit compounds. The finding of this study suggests that these hits can be utilized as the RSV Fprotein inhibitor to prevent the fusion of the viral envelope with the host cells. Further, bench work experiments are required to optimize these hit compounds as RSV Fprotein inhibitors.


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