scholarly journals IN SILICO DESIGN OF POTENTIAL 1, 5-BENZOTHIAZEPINE DERIVATIVES AS AN ANTI - CONVULSANT AGENT BY MOLECULAR DOCKING STUDIES

2019 ◽  
pp. 29-36
Author(s):  
Parjane Smita ◽  
Kunkulol Rahul ◽  
Nandal Dattatray
Keyword(s):  
Hydrogen Bond ◽  
Docking Studies ◽  
Hydrogen Bond Interaction ◽  
Docking Analysis ◽  
Hydrogen Bond Interactions ◽  
Binding Score ◽  
Anticonvulsant Agent ◽  
Significant Area ◽  
Patients With Epilepsy ◽  
2D And 3D

Epilepsy is characterized by the presence of recurrent seizures. A seizure can be defined as “an episodic disturbance of movement, feeling, or consciousness caused by sudden synchronous, inappropriate, and excessive electrical discharges in the cerebral cortex”. One in every three patients with epilepsy is probable to be severely disabled. It is continuing this scenario as an attempt to develop potent and nontoxic anti-convulsant agents. Recently the discovery of benzothiazepine derivatives as an anticonvulsant agent is a significant area for research in medicinal chemistry as it is free from all side effects which is shown by a developed as an anticonvulsant agent. In this paper, we have presented results of 2D, and 3D docking poses studies of a series of 300 (Three series) molecules containing 1,5-benzothiazepine pharmacophore as anti-convulsant agents. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. All the molecules exhibited a binding score in the range of -82.61 to - 118.25 kcal/mol. Most active molecules from Series 1, 2 and 3 exhibited hydrogen bond interactions with LEU282B, LEU282B and LEU282B. Also for the selected standard sodium phenytoin showed the hydrogen bond interaction with LYS637A. It was noted that the docking score of 1a to 10a, 101b to 110b and 201c to 210c was almost the same as that of selected standard sodium phenytoin. The protein showed hydrogen bonding with all synthesized compound showed potential against epilepsy with GABA nergic mechanism.  Keywords: Anti-convulsant; 1,5-benzothiazepine; V-Life MDS 4.3.

scholarly journals Molecular docking analysis of stevioside with AKT and PPARγ

2021 ◽  
Vol 17 (1) ◽  
pp. 283-288
Author(s):  
Abilasha Deenadayalan ◽  
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Docking Studies ◽  
Autodock Vina ◽  
Docking Analysis ◽  
Hydrogen Bond Interactions ◽  
Ppar Γ ◽  
Molecular Docking Analysis

Stevioside is a diterpenoid glycoside consisting of an aglycone (steviol) and three glucose molecules. It is commonly used as an anti-hyperglycemic food because of its non-caloric property. Therefore, it is of interest to document the interactions of stevioside with AKT & PPAR-γ proteins using Autodock Vina PyRx docking techniques. Results of the docking studies indicate that stevioside had more than two hydrogen bond interactions with the AKT and PPAR γ protein for further consideration.

Symmetry constraints, molecular recognition and crystal engineering. Comparative structural studies of urea–butanedioic and urea–E-butanedioic acid (2:1) cocrystals

1996 ◽  
Vol 52 (6) ◽  
pp. 1048-1056 ◽  
Author(s):  
V. Videnova-Adrabińska
Keyword(s):  
Hydrogen Bond ◽  
Crystal Engineering ◽  
Three Dimensional ◽  
Structural Studies ◽  
Hydrogen Bond Interaction ◽  
Space Group ◽  
One Dimensional ◽  
Hydrogen Bond Interactions ◽  
Symmetry Constraints ◽  
Butanedioic Acid

The crystal structures of two urea–dicarboxylic acid (2:1) cocrystals have been determined. Urea–butanedioic acid forms monoclinic crystals, space group P21/c (No. 14), with a = 5.637 (4), b = 8.243 (3), c = 12.258 (3) Å, β = 96.80 (5)°, V = 565.6 (8) Å3, Z = 2. Urea–E-butenedioic acid also forms monoclinic crystals, space group P21/c (No. 14), with a = 5.540 (1), b = 8.227 (1), c = 12.426 (3) Å, β = 97.22 (3)°, V = 561.9 (2) Å3, Z = 2. The geometry and the conformation of both molecular aggregates and the three-dimensional networks formed are very similar. The two strongest hydrogen-bond interactions are constrained in the formation of the heteroaggregates, the third hydrogen-bond interaction is used to self-associate the heteroaggregates in one-dimensional chains, whereas the next three weaker hydrogen bonds interconnect the chains into well organized three-dimensional networks.

scholarly journals Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus Diaporthe mahothocarpus

2021 ◽  
Vol 7 (10) ◽  
pp. 876
Author(s):  
Geum Seok Jeong ◽  
Prima F. Hillman ◽  
Myung-Gyun Kang ◽  
Sungbo Hwang ◽  
Jong-Eun Park ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Tight Binding ◽  
Docking Studies ◽  
Monoamine Oxidase A ◽  
Binding Affinities ◽  
Hydrogen Bond Interaction ◽  
Bond Interaction ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Lichen Fungus

Using 126 endogenous lichen fungus (ELF) extracts, inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) were evaluated. Among them, extract ELF29 of the endogenous fungus Diaporthe mahothocarpus of the lichen Cladonia symphycarpia showed the highest inhibitory activity against hMAO-A. Compounds alternariol (AT), 5′-hydroxy-alternariol (HAT), and mycoepoxydiene (MED), isolated from the extract, had potent inhibitory activities against hMAO-A with IC50 values of 0.020, 0.31, and 8.68 µM, respectively. AT, HAT, and MED are reversible competitive inhibitors of hMAO-A with Ki values of 0.0075, 0.116, and 3.76 µM, respectively. The molecular docking studies suggested that AT, HAT, and MED had higher binding affinities for hMAO-A (−9.1, −6.9, and −5.6 kcal/mol, respectively) than for hMAO-B (−6.3, −5.2, and −3.7 kcal/mol, respectively). The relative tight binding might result from a hydrogen bond interaction of the three compounds with a Tyr444 residue in hMAO-A, whereas no hydrogen bond interaction was proposed in hMAO-B. In silico pharmacokinetics, the three compounds showed high gastrointestinal absorption without violating Lipinski’s five rules, but only MED showed high probability to cross the blood–brain barrier. These results suggest that AT, HAT, and MED are candidates for treating neuropsychiatric disorders, such as depression and cardiovascular disease.

scholarly journals MOLECULAR DOCKING OF ANTITRYPANOSOMAL INHIBITORS FROM EUCALYPTUS TERETICORNIS FOR SLEEPING SICKNESS

2019 ◽  
pp. 191-195
Author(s):  
AARTHI RASHMI B ◽  
HARISHCHANDER A ◽  
PRIYANKA K ◽  
VASANTH NIRMAL BOSCO
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Energy ◽  
Sleeping Sickness ◽  
Betulonic Acid ◽  
Eucalyptus Tereticornis ◽  
Hydrogen Bond Interaction ◽  
Hydrogen Bond Interactions ◽  
Bond Interaction ◽  
Pure Compounds

Objectives: This study aims to investigate the antitrypanosomal inhibitors of Eucalyptus tereticornis for sleeping sickness through molecular docking and studies on Absorption distribution metabolism excursion and toxicology (ADMET). Methods: In silico molecular docking in ArgusLab software and ADMET analysis in AdmetSAR software was performed for the antitrypanosomal inhibitors of E. tereticornis for sleeping sickness. Results: Interactions were studied for the ten proteins responsible for sleeping sickness with the 50 antitrypanosomal inhibitors of E. tereticornis. Docking was performed to see the interaction and the best binding energy of compounds with the proteins involved in sleeping sickness. The docking scores were highest for betulonic acid with −15.66 kcal/mol followed by euglobal with −12.24 kcal/mol, B-pinene with −10.313 kcal/mol, A-pinene with −10.3418 kcal/mol, and the least docking score for P-cymene with −10.6045 kcal/mol. Docking results showed that only betulonic acid and euglobal showed that hydrogen bond interaction was as b-pinene, a-pinene, and p-cymene yielded no hydrogen bond interactions so we will be taking the former docking results for further studies. The best docking result was shown by betulonic acid with trypanothione reductase giving binding energy of −15.66 kcal/mol with hydrogen bond interaction of 2.9, so this result was taken for further analysis. Conclusion: The results of the compound extracted from E. tereticornis will become physiological relevant only when (i) the pure compounds of this plant is available in large quantities; (ii) the Eucalyptus is biochemically stabilized to avoid degradation and enhance absorption in the gastrointestinal tract; and (iii) special delivery methods for this drug to reach the areas of treatment. In this work, the efficacy of E. tereticornis to act against trypanosomal protein was initiated and thus further research in this process would help us to take full advantage of the remedial effects of the compounds extracted from this plant.

Synthesis, Antitubercular Activity, Molecular Modeling and Docking Studies of Novel Thiazolidin-4-One Linked Dinitrobenzamide Derivatives

2020 ◽  
Vol 16 (1) ◽  
pp. 64-71
Author(s):  
Karanveer Singh ◽  
Manish Sinha ◽  
Shruti Kuletha ◽  
Baljeet Kaur ◽  
Amandeep Kaur ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Molecular Modeling ◽  
Antitubercular Activity ◽  
Pharmacophore Modeling ◽  
Docking Studies ◽  
Lead Optimization ◽  
World Health ◽  
Aromatic Moiety ◽  
Hydrogen Bond Interactions ◽  
The World

Background: Tuberculosis is a catastrophe sprawled across the world. The World Health Organization Global Tuberculosis Report 2017 inferred that there were an estimated 10.4 million people suffered from tuberculosis including 490000 Multidrug-Resistant TB (MDR-TB) cases. Several new lead molecules like dinitrobenzamide derivatives were found to be highly active against multidrugresistant strains of M. tuberculosis. To further explore the pharmacophoric space around the dinitobenzamide moiety, a series of compounds have been synthesized by linking it with the thiazolidin- 4-one. The presented work is an effort to study the biological effect of thiazolidin-4-one scaffold on dinitrobenzamide derivatives as antitubercular agents. A molecular modeling study was also performed on the synthesized molecules to reveal the requirements for further lead optimization. Methods: The thiazolidin-4-one linked 3,5-dinitrobenzamide derivatives have been synthesized by onepot three-component condensation reaction of an amine, substituted aldehydes and thioglycolic acid in presence of N, N'-Dicyclohexylcarbodiimide (DCC). These compounds were evaluated against Mycobacterium tuberculosis H37Ra. A pharmacophore modeling approach has been used in order to explore the collection of possible pharmacophore queries of thiazolidin-4-one linked 3, 5-dinitrobenzamide derivatives against M. tuberculosis. The synthesized compounds were docked on to the M. tuberculosis DprE1 enzyme to identify the structural features requirement of these analogs against this potential target of M. tuberculosis. Results: The synthesized compounds showed the antitubercular activity in the range of 6.25-50 μg/ml. The pharmacophore modeling suggests that the presence of aromatic moiety, thiazolidin-4-one ring and one of the nitro groups are significant for inhibiting the enzymatic activity. While docking studies showed that hydrophobic and hydrogen bond interactions of the aromatic moiety and nitro group crucial to inactivate the DprE1 enzyme. Conclusion: The study showed that the linking of thiazolidin-4-one with dinitrobenzamide leads to compounds active against M. tuberculosis. These findings also suggested that further lead optimization would be carried out by focusing on the aromatic system along with electron-rich substituents placed on the thiazolidin-4-one for making better hydrophobic and hydrogen bond interactions with the DprE1 target.

scholarly journals Molecular docking studies of deacetylbisacodyl with intestinal sucrase-maltase enzyme

2017 ◽  
Vol 2 (12) ◽  
pp. 191 ◽  
Author(s):  
Ramchander Merugu ◽  
Uttam Kumar Neerudu ◽  
Karunakar Dasa ◽  
Kalpana V. Singh
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Electrostatic Interactions ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Interaction Study ◽  
Ligand Interaction ◽  
Docking Analysis ◽  
Protein Ligand Interaction ◽  
Intestinal Sucrase

Molecular docking of sucrase-isomaltase with ligand deacetylbisacodyl when subjected to docking analysis using docking server, predicted in-silico result with a free energy of -3.36 Kcal/mol which was agreed well with physiological range for protein-ligand interaction, making bisacodyl probable potent anti-isomaltase molecule. According to docking server Inhibition constant is 5.98Mm. which predicts that the ligand is going to inhibits enzyme and result in a clinically relevant drug interaction with a substrate for the enzyme. Hydrogen bond with bond length 3.45is formed between Pro 64 (A) of target and of ligand, which is again indicative of the docking between target and ligand. Excellent electrostatic interactions of polar, hydrophobic, pi-pi and Van der walls are observed. The proteinligand interaction study showed 6 amino acid residues interaction with the ligand.

Molecular Docking Studies of Indolyl-Benzodioxyl-Chalcone, Pyrrolyl-Benzodioxyl- Chalcone, and Thiophenyl-Benzodioxyl-Chalcone as an Antimalarial Agent

2021 ◽  
Vol 874 ◽  
pp. 136-142
Author(s):  
Kamilia Mustikasari ◽  
Joshua Eka Harap ◽  
Tanto Budi Susilo ◽  
Noer Komari
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Kcal Mole ◽  
Docking Simulations ◽  
Drug Candidates ◽  
Hydrogen Bond Interactions ◽  
New Compounds ◽  
Native Ligand

The drug resistance condition of P. falciparum pose a major challenge in the fight against malaria. This prompts a comprehensive research in an effort to discover new drug candidates. Therefore, chalcone was modified into 24 new compounds, including indolyl-benzodioxyl-chalcone, pyrrolyl-benzodioxyl-chalcone, and thiophenyl-benzodioxyl-chalcone in the course of this study. Moreover, these compounds are commercial malaria mediciations screened for their inhibitory activity using molecular docking simulations. Subsequent results of combined indolyl-benzodioxyl-chalcone and PfDHFR-TS showed the intrinsic indolyl components produced stronger interactions referenced to pyrrolyl-benzodioxyl-chalcone, thiophenyl-benzodioxyl-chalcone, and chloroguanide. Under these circumstances, intense PfDHFR-TS-indolyl-benzodioxyl-chalcone complex was produced with lower binding affinity values (-7.32 to -8.43 kcal/mole) referenced to PfDHFR-TS-pyrrolyl-benzodioxyl-chalcone (-6.38 to -6.68 kcal/mole), PfDHFR-TS-Thiophenyl-benzodioxyl-chalcone (-6.47 to -6.52 kcal/mole), and PfDHFR-TS-chloroguanide (-6.75 kcal/mole). Furthermore, the hydrogen bond interactions developed by indolyl-benzodioxyl-chalcone (7-10) are observably similar to standard chloroguanide compounds and WR99210. These compounds also possess a binding affinity similar to WR99210 (native ligand) and are expected to be potentially anti-malarial candidates.

Docking Studies, Synthesis and Evaluation of Novel Pyrimidin-2-one Derivatives As a Dipeptidyl Peptidase IV Inhibitors

2021 ◽  
pp. 5973-5977
Author(s):  
Prerana A. Chavan ◽  
Shailaja B. Jadhav
Keyword(s):  
Phenyl Group ◽  
Docking Study ◽  
Dipeptidyl Peptidase ◽  
Docking Studies ◽  
Hydrogen Bond Interaction ◽  
Docking Analysis ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase Iv Inhibitors ◽  
Treatment Of Diabetes

Diabetes is a disorder which is characterized by increase in blood glucose level beyond normal value. Now days it is a metabolic disorder and considered as one of the major cause for the death of patients worldwide. Hence there is always a need for the development of newer scaffolds which are useful in treatment of diabetes. In the research computational chemistry plays an important role to discover new possible medicines. In this work, docking analysis has been carried out to study the effects of substituted pyrimidin-2-one on Dipeptidyl peptidase-4 (DPP4). Docking study shows that compound A5 having 2,4-difluorophenyl and 2-hydroxy phenyl group has a potent (IC50 28.13 µM), selective and in vitro efficacious DPP-4 inhibitor. Further molecular modeling revealed compound A5 can fit in the enzyme pocket topologically very well with the pyrimidin-2-one moiety providing hydrogen bond interaction with Glu 205 and Ser 209 of DPP-4. Based on these results, compound A5 might be a promising lead compound for further optimization in the treatment of T2DM.

scholarly journals N-Methyl-2-(1-methyl-3-phenylprop-2-en-1-ylidene)hydrazinecarbothioamide

2014 ◽  
Vol 70 (7) ◽  
pp. o800-o800 ◽  
Author(s):  
Fillipe Vieira Rocha ◽  
Adelino Vieira de Godoy Netto ◽  
Johannes Beck ◽  
Jörg Daniels ◽  
Adriano Bof de Oliveira
Keyword(s):  
Hydrogen Bond ◽  
Torsion Angle ◽  
Title Compound ◽  
Crystal Packing ◽  
Maximum Deviation ◽  
Hydrogen Bond Interaction ◽  
Hydrogen Bond Interactions ◽  
Compound C ◽  
The Mean ◽  
Centrosymmetric Dimers

In the title compound, C12H15N3S, the molecule deviates slightly from planarity, with a maximum deviation from the mean plane of the non-H atoms of 0.2756 (6) Å for the S atom and a torsion angle for the N—N—C—N fragment of −7.04 (16)°. In the crystal, molecules are linked by N—H...S hydrogen-bond interactions, forming centrosymmetric dimers. Additionally, one weak intramolecular N—H...N hydrogen-bond interaction is observed. The crystal packing shows a herringbone arrangement viewed along thecaxis.

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