scholarly journals Synthesis, In Silico Molecular Docking Modeling and Pharmacophore Mapping of (E)-3-(4-Hydroxy-2,6-Dimethoxyphenyl)-1-Phenylprop-2-en-1-One as Potential New Inhibitor of Microsomal Prostaglandin E2 Synthase-1

2020 ◽  
Vol 981 ◽  
pp. 247-252
Author(s):  
Pitipat Sanphetchaloemchok ◽  
Mohd Fadhlizil Fasihi Mohd Aluwi ◽  
Kamal Rullah ◽  
Kok Wai Lam
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Molecular Conformation ◽  
Condensation Reaction ◽  
Docking Simulation ◽  
Pharmacophore Modeling ◽  
Prostaglandin E ◽  
Molecular Docking Simulation ◽  
Anti Inflammatory ◽  
Shed Light

The discovery of potent anti-inflammatory agents through inhibition of prostaglandin E2 (PGE2) via microsomal prostaglandin E2 synthase-1 (mPGES-1) blocking has been proven to be an important game changer in pharmaceutical industry in recent years. In this study, new chalcone derivative has been successfully synthesized via Claisen-Schmidt condensation reaction. The compound was then docked into mPGES-1 active site to predict anti-inflammatory properties through ligand-enzyme interaction investigation. The data collected from in silico molecular docking simulation and pharmacophore modeling studies provide important insight on the molecular conformation and further shed light towards structural modification of the future novel mPGES-1 inhibitor.

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 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.

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.

Design, Molecular docking, Synthesis and Biological evaluation of 5, 7 dimethyl pyrido(2, 3-d)pyrimidin-4-one and 4,5 dihydro pyrazolo (3, 4-d) pyrimidines for cytotoxic activity

2021 ◽  
pp. 3029-3038
Author(s):  
M. Sathish Kumar ◽  
M. Vijey Aanandhi
Keyword(s):  
Molecular Docking ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Hep G2 ◽  
Molecular Docking Simulation ◽  
Hela Cell Lines ◽  
Benzene Diazonium ◽  
Synthesis And Biological Evaluation ◽  
Mcf 7

The fused pyrimidine derivatives are potent tyrosine kinase and thymidylate synthase inhibitors. The compound 3-(4-sulphonyl amino)-2-methyl thio-6-phenyl azo-5, 7-dimethyl pyrido(2,3-d)pyrimidin-4-one was synthesized from Ethyl 2-amino-4,6-dimethylpyridine-3-carboxylate, benzene diazonium chloride, benzene sulphonyl amino isothiocyanate in subsequent reactions. 1-(1, 3-benzothiazol-2-yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidines were synthesized from 1, 3-benzothiazole, 2-thiol, Hydrazine Hydrate, 2-hydrazinyl-1, 3-benzothiazole and aldehydes in subsequent reactions. Twenty-five derivatives pyrimidine scaffolds were designed and performed molecular docking studies for the ability to inhibit the target protein using molecular docking simulation, selective compounds were synthesized and characterized by spectral methods. All the synthesized compounds evaluated for their antioxidant activity and MTT assay exhibited compounds 13c, 13e and 14d can be potential anticancer candidates against MCF-7, Hep G2 and Hela cell lines respectively. Based on all the studies conclude that good agreement was observed between the top-ranked docking scores and top experimental inhibitors when compared with standards ascorbic acid and imatinib. Hence, the compounds could be considered as new anticancer hits for further lead optimization.

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