scholarly journals THE MOLECULAR INTERACTION AND ADMET PREDICTION OF MODIFIED JPH203 AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER: AN IN SILICO RESEARCH

2021 ◽  
pp. 205-209
Author(s):  
HOLIS ABDUL HOLIK ◽  
FAISAL MAULANA IBRAHIM ◽  
ELISHA WIANATALIE ◽  
ARIFUDIN ACHMAD ◽  
AHMAD FARIED ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular Imaging ◽  
Active Site ◽  
Molecular Interaction ◽  
In Silico ◽  
Docking Simulation ◽  
Molecular Docking Simulation ◽  
Docking Score ◽  
Hydrogen Interaction ◽  
Good Potential

Objective: In this study, various types of pharmacokinetic modifying linkers and chelators are combined with JPH203 to obtain the best-docked molecule for prospective radiopharmaceutical kits. Methods: AutoDock 4.2.6 and AutoDockTools 1.5.6 programs was used to do the molecular docking simulation and ADMET prediction was done using VNN-ADMET to predict the pharmacokinetics and toxicity of the ligand. Results: The result of this study showed that JPH203-linker K-NOTA has the best affinity with a docking score of about-10.7 kcal/mol and shows hydrogen interaction with Tyr259, which acts as key residue of the active site. Conclusion: Based on the results, JPH203-linker K-NOTA has good potential as a radiopharmaceutical kit of cancer.

Discovery of Natural Product Compounds as Dengue Virus NS5 Methyltransferase Inhibitor Candidate through in Silico Method

2020 ◽  
Vol 840 ◽  
pp. 270-276
Author(s):  
Anjas Randy Bagastama ◽  
Ahmad Husein Alkaff ◽  
Usman Sumo Friend Tambunan
Keyword(s):  
Molecular Docking ◽  
Dengue Virus ◽  
Natural Product ◽  
In Silico ◽  
Antiviral Agents ◽  
Docking Simulation ◽  
Simulation Method ◽  
Molecular Docking Simulation ◽  
Drug Candidates ◽  
Natural Product Compounds

Dengue is a global health problem which predominantly affected the tropical and subtropical region of Asia, Africa, and America. However, there are no available antiviral agents to treat dengue virus (DENV) infection. This study was conducted to utilize natural product compounds as an inhibitor of NS5 Methyltransferase, a viral protein which plays an essential role in the synthesis of DENV RNA. The natural product compounds were collected from the Universal Natural Product Database (UNPD), totaling 229,000 compounds. The in silico screening of the natural product compounds was performed by molecular docking simulation method, which simulates the interaction of the compounds on the active site of the NS5 methyltransferase. From the molecular docking simulation, about 51 compounds showed better affinity and interaction compared to the standard compound, S-Adenosyl-L-Homocysteine (SAH). Then, a series of pharmacological tests were performed to find the best drug candidates by employing DataWarrior and SwissADME software. Finally, three natural product compounds, namely UNPD98966, UNPD183023, and UNDP104952, were regarded as the best inhibitor against NS5 methyltransferase based on its molecular affinity and interaction. These compounds also showed potential as drug candidates due to their desirable pharmacological properties.

scholarly journals Molecular docking-simulation edge assessment of potential and less-toxic ‘anti- HIV-drug and phyto-flavonoid’ combination against COVID-19

2020 ◽  
Author(s):  
Shasank S. Swain ◽  
Satya R. Singh ◽  
Alaka Sahoo ◽  
Tahziba Hussain ◽  
Sanghamitra Pati
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Study ◽  
Viral Disease ◽  
Hiv Protease ◽  
Dynamics Simulation ◽  
Genome Replication ◽  
Molecular Docking Simulation ◽  
Docking Score ◽  
Anti Hiv

Abstract The emergence of the pandemic coronavirus-2019 (COVID-19) disease by the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) or 2019-novel coronavirus-2019 (2019- nCoV-2019) has created a disease-ridden environment for the entire human community, globally. However, no potent prophylactic therapy is available to control the deadly emerged viral disease. Repurposing of existing antiviral, antiinflammatory, antimalarial drugs is the only option against SARS-CoV-2. But without any clinical evidence, the recommended dose and expected side effects are under debate. As an alternative solution, we proposed a newer hypothesis using the selective, potent anti-HIV drugs and flavonoid class of phytochemicals in combination to balance the potency and toxicity during combat against SARS-CoV-2. Primarily, ten anti-HIV protease inhibitor drugs with ten phyto-flavonoids are selected as ligands for docking study against the putative target, the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, -10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, -10.90 kcal/mol and drug-likeness rating, 0.82), were selected for further analysis in the mixture. Later, the interchanged mutual docking analysis suggested that ‘darunavir-quercetin-3- rhamnoside’ was the most potent and less toxic drug chemical-cocktail/ formulation against SARS-CoV-2-Mpro. Additionally, molecular dynamics simulation, predicted toxicity and pharmacokinetics profiles also support to the hypothesized formulation; mainly, eight strong H- bond interactions were found against SARS-CoV-2-Mpro. Thus, projected molecular docking- simulation based active and lesser toxic ‘anti-HIV-drug-phyto-flavonoid’ therapy could be promoted against SARS-CoV-2.

scholarly journals IN SILICO STUDIES OF (S)-2-AMINO-4-(3,5-DICHLOROPHENYL) BUTANOIC ACID AGAINST LAT1 AS A RADIOTHERANOSTIC AGENT OF CANCER

2021 ◽  
pp. 239-243
Author(s):  
HOLIS ABDUL HOLIK ◽  
FAISAL MAULANA IBRAHIM ◽  
ABIB LATIFU FATAH ◽  
ARIFUDIN ACHMAD ◽  
ACHMAD HUSSEIN SUNDAWA KARTAMIHARDJA
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Simulation ◽  
Butanoic Acid ◽  
Molecular Docking Simulation ◽  
Bifunctional Chelators ◽  
In Silico Studies ◽  
Carrier Molecule ◽  
Human Use ◽  
Adme Profile

Objective: This study aims to obtain a good activity of radiotheranostic kit for cancer which is built by combining (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) with various bifunctional chelators. Methods: This study was conducted through in silico method that consists of molecular docking simulation using AutoDock 4 as well as ADMET prediction using vNN-ADMET and Pre-ADMET. Six bifunctional chelators (i.e. CTPA, DOTA, H2CB-TE2A, H2CB-DO2A, NOTA, and TETA) were conjugated with ADPB as a carrier molecule and further analyzed through molecular docking and ADMET prediction. Results: The results showed that the ADPB-NOTA has the best affinity with the Gibbs free energy (ΔG) of-7.68 kcal/mol with an inhibition constant of 2.36 µM and its ability to bind with the gating residue of LAT1 (ASN258) through hydrogen interactions. Besides that, the ADPB-NOTA compound has a good ADME profile and is predicted to be safe for human use. Conclusion: This study showed that ADPB-NOTA is the most prospective candidate to be used as a radiotheranostic agent.

Synthesis, Cytotoxicity and Molecular Docking Simulation of Novel bis-1,4-Dihydropyridines Linked to Aliphatic or Arene Core via Amide or Ester-Amide Linkages

2020 ◽  
Vol 20 (9) ◽  
pp. 801-816 ◽  
Author(s):  
Amna M. Abdella ◽  
Amr M. Abdelmoniem ◽  
Nada S. Ibrahim ◽  
Salwa M. El-Hallouty ◽  
Ismail A. Abdelhamid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Active Site ◽  
Docking Simulation ◽  
Moderate Activity ◽  
The Novel ◽  
Human Cell Lines ◽  
Molecular Docking Simulation ◽  
Apoptotic Protein ◽  
Acid Catalyzed

Objective: Novel bis(1,4-dihydropyridine-3,5-dicarbonitrile) derivatives linked to aliphatic or aromatic cores via amide or ester-amide linkages were prepared and their structures were confirmed by several spectral tools. Methods: The synthesis of novel N,N'-(alkanediyl)bis(2-(2-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin- 4-yl)phenoxy)acetamide) by acid-catalyzed condensation of the bis-aldehydes with four equivalents of 3-aminocrotononitrile was reported. Results: The structures of the synthesized compounds were confirmed by different spectral tools. The molecular docking stimulation studies indicated that the prepared compounds bind to the active site of cellular inhibitor apoptotic protein (cIAP1-BIR3). MTT assay for the novel bis(1,4-dihydropyridines) was performed on two different human cell lines (A549 and HCT116). Conclusion: Compound 5a showed higher cytotoxic activity against A549. Compound 5d showed moderate activity against HCT116. The rest of compounds indicated lower or no activity against both cell lines.

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