Anticonvulsant Activity, Molecular Modeling and Synthesis of Spirooxindole-4H-Pyran Derivatives using a Novel Reusable Organocatalyst

Abstract Fifteen derivatives of spirooxindole-4H-pyran (A1-A15) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A3 and A12 were the most active compounds and indicated significant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no significant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding affinities as γ-aminobutyric acid-A (GABA‐A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.

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Modeling the Antileukemia Activity of Ellipticine-Related Compounds: QSAR and Molecular Docking Study

Molecules ◽

10.3390/molecules25010024 ◽

2019 ◽

Vol 25 (1) ◽

pp. 24 ◽

Cited By ~ 3

Author(s):

Edgar Márquez ◽

José R. Mora ◽

Virginia Flores-Morales ◽

Daniel Insuasty ◽

Luis Calle

Keyword(s):

Molecular Structure ◽

Binding Free Energy ◽

Docking Study ◽

Quantitative Structure Activity Relationship ◽

Quantitative Structure ◽

Molecular Docking Study ◽

Modeling Simulation ◽

Structure Activity ◽

Related Compounds ◽

Cancer Activity

The antileukemia cancer activity of organic compounds analogous to ellipticine representes a critical endpoint in the understanding of this dramatic disease. A molecular modeling simulation on a dataset of 23 compounds, all of which comply with Lipinski’s rules and have a structure analogous to ellipticine, was performed using the quantitative structure activity relationship (QSAR) technique, followed by a detailed docking study on three different proteins significantly involved in this disease (PDB IDs: SYK, PI3K and BTK). As a result, a model with only four descriptors (HOMO, softness, AC1RABAMBID, and TS1KFABMID) was found to be robust enough for prediction of the antileukemia activity of the compounds studied in this work, with an R2 of 0.899 and Q2 of 0.730. A favorable interaction between the compounds and their target proteins was found in all cases; in particular, compounds 9 and 22 showed high activity and binding free energy values of around −10 kcal/mol. Theses compounds were evaluated in detail based on their molecular structure, and some modifications are suggested herein to enhance their biological activity. In particular, compounds 22_1, 22_2, 9_1, and 9_2 are indicated as possible new, potent ellipticine derivatives to be synthesized and biologically tested.

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MODULATORY ANTI- DIARRHEAL EFFECTS OF ASCORBIC ACID IN SWISS ALBINO MICE

Khulna University Studies ◽

10.53808/kus.2021.18.01.2103-l ◽

2021 ◽

Vol 18 (1) ◽

pp. 9-17

Keyword(s):

Ascorbic Acid ◽

Adrenergic Receptor ◽

Castor Oil ◽

Docking Study ◽

Binding Affinities ◽

Molecular Docking Study ◽

Receptor Blocking ◽

Swiss Mice ◽

Mixed Groups ◽

The Impact

Ascorbic acid (AA) has been reported for the management of diarrhea. The anti-diarrheal potential and modulatory activities of AA on some commonly used anti-diarrheal drugs were investigated. For this purpose, the activities of AA on castor oil-induced diarrhea in Swiss mice were examined. As standard anti-diarrheal agents, we used prazosin, propranolol, loperamide, and nifedipine with or without AA. The results revealed that AA at 25 mg/kg (i.p.) and all other standard drugs exhibited significant (p < 0.05) diarrheal attenuating activities in mice. However, the impact was more pronounced in the loperamide and propranolol groups. AA administrated with prazosin and propranolol had a higher rate of latent periods and a lower rate of diarrheic secretion during the study period (4 h) than that of the other single or mixed groups. Furthermore, a molecular docking study illustrated that AA displayed good binding affinities with (α1) (–5.2 Kcal/mol), α2b (–5.4 Kcal/mol), α2c (-5.6 Kcal/mol), β1(–5.3 Kcal/mol) and β2(–6.4 Kcal/mol) adrenoceptors. Of note, AA exerted a significant anti-diarrheal effect and it was seen to modulate the anti-diarrheal effects of α- and β-adrenergic receptor blocking agents in Swiss mice.

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Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

International Journal of Medicinal Chemistry ◽

10.1155/2018/9139786 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Musab Mohamed Ibrahim ◽

Tilal Elsaman ◽

Mosab Yahya Al-Nour

Keyword(s):

Virtual Screening ◽

Condensation Reaction ◽

Docking Study ◽

Positive Control ◽

Inflammatory Activity ◽

Molecular Docking Study ◽

Design Synthesis ◽

Chemical Structures ◽

Anti Inflammatory

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff’s bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff’s condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

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An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn

Pharmaceuticals ◽

10.3390/ph11030072 ◽

2018 ◽

Vol 11 (3) ◽

pp. 72 ◽

Cited By ~ 10

Author(s):

Mayara Teles Fujishima ◽

Nayara Silva ◽

Ryan Ramos ◽

Elenilze Batista Ferreira ◽

Kelton Santos ◽

...

Keyword(s):

Molecular Docking ◽

Xanthine Oxidase ◽

Quantum Chemical ◽

Binding Free Energy ◽

Chemical Constituents ◽

Docking Study ◽

Antioxidant Potential ◽

Molecular Docking Study ◽

Hydroalcoholic Extract ◽

Curatella Americana

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital’s (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals.

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Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds

Open Chemistry ◽

10.1515/chem-2019-0069 ◽

2019 ◽

Vol 17 (1) ◽

pp. 621-628 ◽

Cited By ~ 1

Author(s):

Mahboob Alam ◽

Youngwon Kim ◽

Soonheum Park

Keyword(s):

Molecular Docking ◽

Binding Free Energy ◽

Docking Study ◽

Herbicidal Activity ◽

Phosphorus Compounds ◽

Moderate Activity ◽

Spectroscopic Techniques ◽

Molecular Docking Study ◽

Mycelium Growth ◽

Phosphorus Containing

AbstractPhosphorus containing steroidal derivatives such as 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5-ene and 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5,22-diene were designed, synthesized and characterized using spectroscopic techniques (IR, 1H, 13C & 31P NMR, HRMS) and elemental analysis. The fungicidal and herbicidal studies of the compounds were performed and the experimental outcomes showed that compound 4 showed a good fungicidal activity against mycelium growth of fungi, while in the case of herbicidal activity, both compounds show a moderate activity compared to the commercial drug; Atrazine. The binding free energy of active compound 4 to the receptor named 4-Hydroxyphenylpyruvate dioxygenase (HPPD) was calculated using the molecular docking study. The HPPD is one of the most effective targets of plants for the herbicide study.

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Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

Pharmaceuticals ◽

10.3390/ph12010020 ◽

2019 ◽

Vol 12 (1) ◽

pp. 20 ◽

Cited By ~ 9

Author(s):

Ryan Ramos ◽

Josivan Costa ◽

Rai Silva ◽

Glauber da Costa ◽

Alex Rodrigues ◽

...

Keyword(s):

Virtual Screening ◽

Binding Free Energy ◽

Structural Similarity ◽

Docking Study ◽

Molecular Docking Study ◽

Chemical Structures ◽

Biological Insecticide ◽

Pass Online ◽

Acetylcholinesterase Enzyme ◽

Potential Inhibitors

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.

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Molecular docking study and development of an empirical binding free energy model for phosphodiesterase 4 inhibitors

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2006.05.017 ◽

2006 ◽

Vol 14 (17) ◽

pp. 6001-6011 ◽

Cited By ~ 11

Author(s):

Fernanda G. Oliveira ◽

Carlos M.R. Sant’Anna ◽

Ernesto R. Caffarena ◽

Laurent E. Dardenne ◽

Eliezer J. Barreiro

Keyword(s):

Free Energy ◽

Molecular Docking ◽

Binding Free Energy ◽

Docking Study ◽

Energy Model ◽

Molecular Docking Study ◽

Phosphodiesterase 4 ◽

Phosphodiesterase 4 Inhibitors ◽

Free Energy Model

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Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

Trends in Sciences ◽

10.48048/tis.2021.39 ◽

2021 ◽

Vol 18 (21) ◽

pp. 39

Author(s):

Mardi Santoso ◽

Muhammad Riza Ghulam Fahmi ◽

Yehezkiel Steven Kurniawan ◽

Taslim Ersam ◽

Sri Fatmawati ◽

...

Keyword(s):

Hydrogen Bonding ◽

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Active Site ◽

Antitubercular Activity ◽

Docking Study ◽

Positive Control ◽

Tuberculosis H37rv ◽

Molecular Docking Study

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

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Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study

10.20944/preprints202004.0102.v3 ◽

2020 ◽

Cited By ~ 2

Author(s):

Trina Ekawati Tallei ◽

Sefren Geiner Tumilaar ◽

Nurdjannah Jane Niode ◽

Fatimawali Fatimawali ◽

Billy Johnson Kepel ◽

...

Keyword(s):

Free Energy ◽

Molecular Docking ◽

Bioactive Compounds ◽

Binding Free Energy ◽

Epigallocatechin Gallate ◽

Docking Study ◽

Molecular Docking Study ◽

Ligand Complex ◽

Main Protease ◽

Glycoprotein Inhibitors

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (Mpro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

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Molecular Docking Evaluation of Some Natural Phenolic Compounds as Aldose Reductase Inhibitors for Diabetic Complications

Journal of Pharmaceutical Technology Research and Management ◽

10.15415/jptrm.2017.52009 ◽

2017 ◽

Vol 5 (2) ◽

pp. 135-148 ◽

Cited By ~ 1

Author(s):

Ajmer Singh Grewal ◽

Neelam Sharma ◽

Sukhbir Singh ◽

Sandeep Arora

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Diabetic Complications ◽

Binding Free Energy ◽

Docking Study ◽

Polyol Pathway ◽

Binding Modes ◽

Active Site Residues ◽

Molecular Docking Study ◽

Natural Phenols

The enzyme aldose reductase (AR) is a member of aldoketoreductase super-family which catalyzes the formation of sorbitol from glucose through polyol pathway of glucose catabolism. Reduced sorbitol production via polyol pathway due to AR inhibition is a target of choice for controlling major complications of diabetes. Epalrestat is the only commercially available inhibitor of AR till date,thus, there is a great need to search for more economical, nontoxic and safer inhibitors of AR enzyme. Flavonoids,the polyphenol compounds in plants have been reported for inhibitory effects against AR. The objective of this study is to explore the binding modes of naturalphenolic compounds with AR to design safer natural drugs as alternatives to synthetic drugs. We conducted a molecular docking study on some naturalphenolic compounds with AR enzyme in complex with the synthetic inhibitor. The overlay of the docked pose of the selected natural phenols with the ARreference inhibitor complex showed that the selected natural compounds have the similar binding pattern with the active site residues of the enzyme as that of co-crystallized inhibitor. The results of docking study showed the best binding affinity of AR with that of 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid and butein, having the lowest binding free energy of –9.8 kcal/mol and–9.7 kcal/mol, respectively. This information can be utilized to design potent, economical and non-toxic natural AR inhibitors from natural phenols for the therapeutics of diabetic complications.

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