scholarly journals SYNTHESIS, CHARACTERIZATION, AND MOLECULAR DOCKING ANALYSIS OF PROLINE (PYRROLIDINE 2-CARBOXYLIC ACID) AND PROLINAMIDE (PYRROLIDINE 2-CARBOXYLIC ACID AMIDE) ISOMERS AS BACTERIAL COLLAGENASE INHIBITORS

2019 ◽  
Vol 12 (1) ◽  
pp. 487
Author(s):  
Kavya Sundararaju ◽  
Ramesh Kumar Chidambaram ◽  
Radhakrishnan Narayanaswamy
Keyword(s):  
Carboxylic Acid ◽  
Acid Amide ◽  
Docking Studies ◽  
Physicochemical Analysis ◽  
Lipinski’S Rule ◽  
Bacterial Collagenase ◽  
Brain Barrier Permeability ◽  
Lipinski’S Rule Of Five ◽  
Photoaging Of Skin

Objectives: D-proline is an isomer of L-proline, naturally occurring amino acid. Apart from this, several proline homologs and analogs are available in nature. For instance, hydroxyproline one of proline analog plays a key role in collagen function. Inhibition of collagenase activity plays a significant role in protecting the unbalanced turnover of collagen, caused due to inflammation and photoaging of skin. This prompted us to carry out the study on proline and prolinamide isomers.Methods: These proline and prolinamide isomers were evaluated on the docking behavior of bacterial collagenase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism and excretion (ADME) analysis, synthesis, and characterization of four prolinamide isomers were also carried out.Results: All the four synthesized prolinamide isomers showed >90% yield. The molecular physicochemical analysis revealed that proline and prolinamide isomers showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis showed that prolinamide isomers predicated to have blood–brain barrier permeability. Docking studies revealed that D (S, R) prolinamide isomer showed the maximum atomic contact energy (−115.09 kcal/mol) with that of Clostridium histolyticum collagenase.Conclusion: Thus, the present study showed the potential of proline and prolinamide isomers as collagenase inhibitors.

scholarly journals SYNTHESIS, CHARACTERIZATION, AND MOLECULAR DOCKING ANALYSIS OF PROLINE (PYRROLIDINE 2-CARBOXYLIC ACID) AND PROLINAMIDE (PYRROLIDINE 2-CARBOXYLIC ACID AMIDE) ISOMERS AS BACTERIAL COLLAGENASE INHIBITORS

2019 ◽  
Vol 12 (1) ◽  
pp. 487
Author(s):  
Kavya Sundararaju ◽  
Ramesh Kumar Chidambaram ◽  
Radhakrishnan Narayanaswamy
Keyword(s):  
Carboxylic Acid ◽  
Acid Amide ◽  
Docking Studies ◽  
Physicochemical Analysis ◽  
Lipinski’S Rule ◽  
Bacterial Collagenase ◽  
Brain Barrier Permeability ◽  
Lipinski’S Rule Of Five ◽  
Photoaging Of Skin

Objectives: D-proline is an isomer of L-proline, naturally occurring amino acid. Apart from this, several proline homologs and analogs are available in nature. For instance, hydroxyproline one of proline analog plays a key role in collagen function. Inhibition of collagenase activity plays a significant role in protecting the unbalanced turnover of collagen, caused due to inflammation and photoaging of skin. This prompted us to carry out the study on proline and prolinamide isomers.Methods: These proline and prolinamide isomers were evaluated on the docking behavior of bacterial collagenase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism and excretion (ADME) analysis, synthesis, and characterization of four prolinamide isomers were also carried out.Results: All the four synthesized prolinamide isomers showed >90% yield. The molecular physicochemical analysis revealed that proline and prolinamide isomers showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis showed that prolinamide isomers predicated to have blood–brain barrier permeability. Docking studies revealed that D (S, R) prolinamide isomer showed the maximum atomic contact energy (−115.09 kcal/mol) with that of Clostridium histolyticum collagenase.Conclusion: Thus, the present study showed the potential of proline and prolinamide isomers as collagenase inhibitors.

scholarly journals PREDICTING THE BIODEGRADABILITY NATURE OF IMIDAZOLE AND ITS DERIVATIVES BY MODULATING TWO HISTIDINE DEGRADATION ENZYMES (UROCANASE AND FORMIMINOGLUTAMASE) ACTIVITIES

2017 ◽  
Vol 10 (11) ◽  
pp. 383 ◽  
Author(s):  
Vijayakumar Veeraragavan ◽  
Radhakrishnan Narayanaswamy ◽  
Rameshkumar Chidambaram
Keyword(s):  
Cytochrome P450 ◽  
Imidazole Ring ◽  
Degradation Pathway ◽  
Docking Studies ◽  
Physicochemical Analysis ◽  
Cytochrome P450 1A2 ◽  
Lipinski’S Rule ◽  
Inhibition Effect ◽  
Ring Compounds ◽  
Lipinski’S Rule Of Five

Objectives: The biodegradation pathway of substituted imidazole ring compounds has been reported to have close analogy to the histidine degradation pathway. This prompted the present study to be carried out on 12 selected imidazole and its derivatives which are 1-imidazole, 1, 2-dimethylimidazole, 1-ethyl imidazole, 2-ethyl-4-methylimidazole, 2-isopropylimidazole, 2-Isopropyl-4-nitro-1H-imidazole, 1-methylimidazole, 2-methyl-5-nitroimidazole, 2-methyl-1-vinylimidazole, 1-nitro imidazole, 1-phenyl imidazole, and 1-vinylimidazole.Methods: The imidazole and its derivatives were evaluated on the docking behavior of urocanase and formiminoglutamase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses (ADME) were done.Results: The molecular physicochemical analysis revealed that all the tested ligands showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis showed that 1-phenylimidazole alone predicated to have cytochrome P450 1A2 inhibition effect. Docking studies revealed that 1-nitroimidazole showed the least atomic contact energy with both targeted enzymes (urocanase and FIGase).Conclusion: Inhibition of both enzymes (urocanase and FIGase) might show poor biodegradability nature. Thus, we can predict biodegradability nature of imidazloe and its derivatives by modulating two histidine degradation enzymes activities.

scholarly journals Molecular Docking Studies of Flavonoids from Andrographis paniculata as Potential Acetylcholinesterase, Butyrylcholinesterase and Monoamine Oxidase Inhibitors Towards the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 11 (3) ◽  
pp. 9871-9879
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors ◽  
Andrographis Paniculata ◽  
Lipinski’S Rule ◽  
Bioinformatic Tools ◽  
Pubchem Database ◽  
Lipinski’S Rule Of Five

Neurodegenerative diseases have been characterized by loss of neuron structures as well as their functions. This study was designed to assess molecular docking of flavonoids from Andrographis paniculata as potential acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase inhibitors in the treatment of neurodegenerative diseases. Eight identified possible inhibitors of acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase from Andrographis paniculata were retrieved from the PubChem database. The molecular docking, ADMET, and Lipinski’s rule of five were examined using different bioinformatic tools. It was shown that only rutin has the highest binding affinity (-12.6 kcal/mol) than the standard used. ADMET results demonstrated that all the eight compounds are druggable candidates except rutin. Also, only tangeritin has a blood-brain barrier (BBB) permeation potential. Hence, it can be deduced that all flavonoid compounds from Andrographis paniculata are orally druggable, which can make them useful in the treatment of neurodegenerative diseases better than donepezil.

scholarly journals Insilico Analysis of PHB from Halophiles for potential Bio-medical applications

2019 ◽  
pp. 211-218
Author(s):  
Vinod. P S ◽  
Neha Guttikonda ◽  
Snehal. M. Mathe ◽  
M B Sulochana
Keyword(s):  
Carbon Dioxide ◽  
Nuclear Magnetic Resonance ◽  
Drug Carrier ◽  
Halophilic Bacteria ◽  
Docking Studies ◽  
Medical Applications ◽  
Hydroxybutyric Acid ◽  
Lipinski’S Rule ◽  
Toxicity Analysis

Polyhydroxybutyrate (PHB) is an important biopolymer accumulated by halophilic organisms. PHA is a family of polyesters is accumulated as granules in the cell of bacteria. Polyhydroxybutyrate (PHB) can be used as an alternative polymer to polylactide-glycolides for drug carrier production. It is a linear homopolymer biosynthesized by various strains of bacteria by condensation of D (-)-B-hydroxybutyric acid and used as an energy and carbon source. PHB can be obtained by extraction from bacteria or by chemical synthesis. To be suitable as drug carrier the PHB (polymer) has to be biocompatible, biodegradable in certain applications, and nontoxic. PHB seems to be biocompatible and biodegrades readily to carbon dioxide in bacteria; however, in humans, the reports are few and contradictory. The PHB was extracted from halophilic bacteria. The structural characterization of PHB was done by using NMR (nuclear magnetic resonance). To genenerate SMILES the structure were drawn in MarvinSketch. The PHB were screened based on the Lipinski’s rule of 5. The PHB molecule was subjected to the toxicity analysis and those that passed the toxicity test analyzed for docking studies.

scholarly journals Promising inhibitors against main protease of SARS CoV-2 from medicinal plants: In silico identification

2021 ◽  
Vol 72 (2) ◽  
pp. 159-169
Author(s):  
OLUWAKEMI EBENEZER ◽  
MICHAEL SHAPI
Keyword(s):  
Medicinal Plants ◽  
Binding Affinity ◽  
In Silico ◽  
Complex Analysis ◽  
Docking Studies ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Pharmacokinetic Properties ◽  
Lipinski’S Rule Of Five ◽  
In Silico Identification

Abstract Some compounds reported as active against SARS CoV were selected, and docking studies were performed using the main protease of SARS CoV-2 as the receptor. The docked complex analysis shows that the ligands selectively bind with the target residues and binding affinity of amentoflavone (–10.1 kcal mol–1), isotheaflavin-3’-gallate (–9.8 kcal mol–1), tomentin A and D (–8.0 and –8.8 kcal mol–1), theaflavin-3,3’-digallate (–8.6 kcal mol–1), papyriflavonol A (–8.4 kcal mol–1), iguesterin (–8.0 kcal mol–1) and savinin (–8.3 kcal mol–1) were ranked above the binding affinity of the reference, co-crystal ligand, ML188, a furan-2-carboxamide-based compound. To pinpoint the drug-like compound among the top-ranked compounds, the Lipinski’s rule of five and pharmacokinetic properties of all the selected compounds were evaluated. The results detailed that savinin exhibits high gastrointestinal absorption and can penetrate through the blood-brain barrier. Also, modifying these natural scaffolds with excellent binding affinity may lead to discovering of anti-SARS CoV agents with promising safety profiles.

scholarly journals MOLECULAR DOCKING ANALYSIS OF THIRTEEN COMPOUNDS AS MODULATOR OF IONOTROPIC GLUTAMATE RECEPTOR

2018 ◽  
Vol 11 (11) ◽  
pp. 114
Author(s):  
Radhakrishnan Narayanaswamy ◽  
Merry Hailu
Keyword(s):  
Docking Studies ◽  
Ionotropic Glutamate Receptors ◽  
Ionotropic Glutamate Receptor ◽  
Docking Analysis ◽  
Lipinski’S Rule ◽  
Pathological Conditions ◽  
Parkinson’S Diseases ◽  
Lipinski’S Rule Of Five ◽  
6 Hydroxydopamine ◽  
And Function

Objectives: Ionotropic glutamate receptors (iGluRs) play a key role in the development and function of the nervous system. They also play an important in memory and learning process. They are implicated in various pathological conditions such as Alzheimer’s, Epilepsy, Huntington’s, and Parkinson’s diseases. This prompted us to carry out the present study on 13 selected compounds.Methods: These 13 compounds were evaluated on the docking behavior of iGluR-2 (iGluR2) using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses were also carried out.Results: The molecular physiochemical analysis revealed that all the 13 ligands showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis showed that all the ligands (except ligands 1 and 12) predicated to have high gastrointestinal absorption property. Docking studies revealed that ligand 8 (dopamine) showed the highest atomic contact energy (ACE) (−78.14 kcal/mol), while ligand 9 (6-hydroxydopamine) showed the least ACE (−14.34 kcal/mol) with that of iGluR2. Similarly, ligand 8 (dopamine) has shown to interact with Ser 142 amino acid residue of iGluR2.Conclusion: Thus, the present study showed the potential of 13 compounds as a modulator of iGluR-2.

scholarly journals Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Suhaib Shekfeh ◽  
Murad Abualhasan ◽  
Ahmad M. Eid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Alpha Amylase ◽  
In Vivo Evaluation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Lipase Enzyme ◽  
Lipinski’S Rule Of Five

AbstractCurrently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.

scholarly journals In silico analysis of Glycogen synthase kinase 3-beta (GSK-3β) as aflatoxin binder

2019 ◽  
Vol 12 (3) ◽  
pp. 1449-1456
Keyword(s):  
Glycogen Synthase ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Aspergillus Nomius ◽  
Gsk 3Β ◽  
Silico Analysis

Aflatoxins are secondary metabolites of certain fungi like Aspergillus flavus, Aspergillus niger, Aspergillus nomius and Aspergillus parasiticus. Food products like cereals, milk, milk products, nuts, oilseeds and spices are reported for aflatoxins contamination. Among the fourteen aflatoxin types reported so far, aflatoxins B1, B2, G1, G2, M1, and M2 are commonly studied. Aflatoxins are known to cause various diseases including aflatoxicosis in livestock and domestic animals and cancer in humans. Recently aflatoxin B1 has reported binding with Glycogen synthase kinase 3-beta (GSK-3β). This prompted to carry out the present study, where Glycogen synthase kinase 3-beta (GSK-3β) was evaluated on the docking behaviour of 13 aflatoxin analogues using Patch Dock. In addition, molecular physicochemical, drug-likeness, ADME (Absorption, Distribution, Metabolism and Excretion analyses) were also carried out. The molecular physiochemical analysis revealed that aflatoxin analogue showed nil violation and complied well with the Lipinski’s rule of five. ADME analysis indicates all thirteen aflatoxin analogue predicated to have high gastro-intestine (GI) absorption property. Docking studies, with GSK-3β, revealed that aflatoxin G2 analogue showed the largest atomic contact energy (-224.82 kcal/mol) and Aflatoxin P1 analogue had the least (-160.33 kcal/mol). In addition, aflatoxin P1 analogue has interacted with Asp200 amino acid residue of GSK-3β. Thus, the present study showed the potential of GSK-3β as aflatoxin binder.

Novel 7-substituted Fluoroquinolone Citrate Conjugates as Powerful Antibacterial and Anticancer Agents: Synthesis and Molecular Docking Studies

2019 ◽  
Vol 23 (18) ◽  
pp. 1992-2003
Author(s):  
Tejeswara R. Allaka ◽  
Jaya S. Anireddy
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Line ◽  
Anticancer Agents ◽  
Docking Studies ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Lipinski’S Rule ◽  
Ic50 Value ◽  
Pharmacokinetic Properties ◽  
Lipinski’S Rule Of Five

In this study, the synthesis and evaluation of norfloxacin analogues of dimethyl citrate conjugates were described and their antibacterial and anticancer activities were assessed. The cognate 7-substituted norfloxacin citrate conjugates are active against various strains of bacteria, including MRSA (methicillin-resistant Staphylococcus aureus) with higher activity than ciprofloxacin. Screening results indicated that compound 10 possessed good antibacterial activity against several microorganisms, with MIC values in the range of 0.16-0.35 mg/mL and MBCs in the range of 0.55-0.84 mg/mL. Experiments indicated that 9 demonstrated the most significant activity towards the HCT-15 cell line with IC50 value 8.2 ± 0.139 and against the HT-29 cell line with IC50 8.9 ± 0.122. The title compounds were also evaluated for determining the molecular and pharmacokinetic properties and drug-likeness model scores by using the Molinspiration-2008 and MolSoft-2007 softwares. The region isomeric conjugates followed the Lipinski’s rule of five can be considered as potential antibacterial and anticancer bioavailable oral leads. Compounds 9 and 10 possessed maximum drug-likeness scores. The docking pose interactions of target compounds with the active site of enzyme PDB: 2ZCS of Staphylococcus aureus were estimated by using Autodock 4.2, to calculate the affinity, binding orientation of the ligand with the target protein and to explore the finest conformations. The target compounds, 7, 8, 9, 10, with protein, were loaded separately into Auto dock tools (ADT) and evaluated. The citrate conjugates, 8, 9, showed better docking scores with amino acids Lys17, Ser21, Val268, Lys273 and Arg171, Arg265, Val268, Val273 with the binding energy -5.70, -5.57 kcal/mol and dissociation constant 66.62, 82.13 µM respectively.

scholarly journals MOLECULAR DOCKING STUDY OF NEUROPROTECTIVEPLANT-DERIVED BIOMOLECULES IN PARKINSON’S DISEASE

2017 ◽  
Vol 9 (9) ◽  
pp. 149 ◽  
Author(s):  
Saurabh Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Neuroprotective Activity ◽  
Therapeutic Window ◽  
Molecular Docking Study ◽  
Altered Expression ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Free Energy Of Binding

Objective: The objective of this study was to explore the therapeutic role of biomolecules in targeting the altered expression of Parkin in PD pathogenesis.Methods: We employed various in silico tools such as drug-likeness parameters, namely, Lipinski filter analysis, Muscle tool for phylogenetic analysis, Castp Server for active site prediction, molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.Results: Our results show that neuroprotective activity of Quercetin to be most effective and can provide their possible clinical relevance in PD. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found Quercetin to be most effective amongst four biomolecules in modulating Parkin based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area in a course of docking studies.Conclusion: This research could provide a potential therapeutic window for the treatment of PD.

Sign in / Sign up

Export Citation Format

Share Document