Synthesis and molecular docking study of novel alizarin derivatives containing phosphoryl amino acid moiety as potential antitumor agents

AbstractObjectivesMatrix metalloproteinase-13 (MMP-13) has been reported to be involved in different biological processes such as degradation of extracellular matrix proteins, activating or degrading some significant regulatory proteins, wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization, ossification, cell migration, and tumor cell invasion. Further, MMP-13 participates in many oral diseases such as tooth decay, gingivitis, and degradation of enamel and tissue around the implant. In addition, inhibition of MMP-13 has shown therapeutic properties for Alzheimer’s disease (AD). We performed molecular docking to assess the binding affinity of 29 flavonoid compounds with the MMP-13. Additionally, pharmacokinetic and toxicity characteristics of the top-ranked flavonoids were studied. The current study also intended to identify the most important amino acids involved in the inhibition of MMP-13 based on topological feature (degree) in the ligand-amino acid network for MMP-13.MethodsMolecular docking and network analysis were studied using AutoDock and Cytoscape software, respectively. Pharmacokinetic and toxicity characteristics of compounds were predicted using bioinformatics web tools.ResultsThe results revealed that nine of the studied flavonoids had considerable estimated free energy of binding and inhibition constant: Rutin, nicotiflorin, orientin, vitexin, apigenin-7-glucoside, quercitrin, isoquercitrin, quercitrin-3-rhamnoside, and vicenin-2. Proline-242 was found to be the most important amino acid inhibiting the enzyme.ConclusionsThe results of the current study may be helpful in the prevention and therapeutic procedures of many disorders such as cancer, tooth caries, and AD. Nevertheless, validation tests are required in the future.

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Synthesis, structural characterization, molecular docking study, biological activity of carbon monoxide release molecules as potent antitumor agents

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104621 ◽

2021 ◽

pp. 104621

Author(s):

Hua-Peng Liu ◽

Yuan Liao ◽

Ming-Zhe Ren ◽

Zheng-Jun Quan ◽

Xi-Cun Wang

Keyword(s):

Carbon Monoxide ◽

Biological Activity ◽

Molecular Docking ◽

Structural Characterization ◽

Antitumor Agents ◽

Docking Study ◽

Molecular Docking Study

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Study of Molecular Docking of Chalcone Analoque Compound as Inhibitors for Liver Cancer Cells HepG2

Computer Engineering and Applications Journal ◽

10.18495/comengapp.v7i2.260 ◽

2018 ◽

Vol 7 (2) ◽

pp. 147-158

Author(s):

Neni Frimayanti ◽

Enda Mora ◽

Rizki Anugrah

Keyword(s):

Molecular Docking ◽

Amino Acid ◽

Liver Cancer ◽

Docking Study ◽

Positive Control ◽

Crystallographic Structure ◽

Amino Acid Residues ◽

Autodock Vina ◽

Molecular Docking Study ◽

Liver Cancer Cells

Molecular docking study using chalcone analogue compounds with proteins target from modeling crystallographic structure of Tyrosine kinase enzymes with code 1T46 was carried out with the aid of a computer using the AutoDock Vina program. The aim this study to determine the activity of 5 chalcone analogue compounds obtained from previous studies and 3 chalcone analogues which were modified as inhibitors of liver cancer using 5-fluorouracil as a positive control. Based on the docking results, it has been carried out and shown those compounds 1, 2, and 3 have the potential as the active inhibitors againts HepG2 liver cancer with a successive affinity of -10.1 kcal/mol, -9.7 kcal/mol, and - 9.6 kcal/mol, respectively. For the modified chalcone analogue compounds, compound 8 has the best results with an affinity value of -8.3 kcal/mol and this compound also has six amino acid residues which are the same as 5-flourouracyl (i.e. positive control).

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COUMARIN ANALOGUES AS A POTENTIAL INHIBITOR OF LEISHMANIASIS: A MULTI-TARGETING PROTEIN INHIBITION APPROACH BY MOLECULAR DOCKING

Universal Journal of Pharmaceutical Research ◽

10.22270/ujpr.v4i3.268 ◽

2019 ◽

Author(s):

Kapish Kapoor

Keyword(s):

Molecular Docking ◽

Amino Acid ◽

Active Compound ◽

Active Site ◽

Therapeutic Potential ◽

Docking Study ◽

Developed Countries ◽

Molecular Docking Study

Leishmaniasis is one of the most dreadful diseases as a leading cause of death in most of the developed countries. In the given study molecular docking study was performed on the library of coumarin analogues as anti-leishmaniasis agents. Total 300 coumarins analogues were taken from Pubmed and were studied using a molecular docking study on trypanothione reductase from Leishmania infantum (PDB code: 2JK6 and 2P18) and Leishmania mexicana (PDB code: 3PP7). Molecular docking result revealed that most active compound COU-130 and COU-220 bind to the active site of the protein with amino acids present in the various proteins. In PDB 2JK6 the active compound binds to the amino acid thr-51 and ser-14 were binding to the active site, and in PDB 3PP7 the active compound binds amino acid thr-26 and in PDB 2P18 the active compound binds to the amino acid phe-219 and try-212. Further in vitro and in vivo study of selected coumarin analogues can be studied for their therapeutic potential in treating leishmaniasis.

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Synthesis, Molecular Docking and Pharmacological Investigation of Some 4-Methylphenylsulphamoyl Carboxylic Acid Analogs

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.3157 ◽

2020 ◽

Vol 11 (4) ◽

pp. 5357-5366

Author(s):

Melford C Egbujor ◽

Uchechukwu C Okoro ◽

Sunday N Okafor ◽

Ifeanyi S Amasiatu ◽

Ugochukwu B Amadi ◽

...

Keyword(s):

Molecular Docking ◽

Amino Acid ◽

Analytical Data ◽

Methyl Chloride ◽

Docking Study ◽

Molecular Docking Study ◽

Binding Interaction ◽

Sulfa Drug ◽

Lipinski’S Rule ◽

Anti Oxidant

Compounds bearing and amino acid moieties are considered the basis for sulfa drug development. The synthesis of 4-methylphenylsulphamoyl acids and the evaluation of their pharmacological activities are reported. The synthesis of these compounds was accomplished by the reaction of various acids and 4-methyl chloride in basic aqueous solution. Structures were confirmed by FTIR, 1HNMR, 13CNMR spectra and elemental analytical data. Molecular docking interactions of the analogues were determined using PyRx. In the in antimicrobial activity analysis, compounds 1, 3, 5and 7 had antimicrobial inhibitory concentration range of 0.5-1.0mg/ml comparable with 0.1-2.0mg/ml of and . In the in anti-oxidant activity study compounds 1, 2and 6displayed half-maximal inhibitory concentrations (IC50) of 1.104±0.001 /ml, 1.159±0.002µg/ml and1.240±0.001µg/ml respectively comparable with 0.999±0.002µg/ml of acid. In the molecular docking study, compound 4 had a strong 2D binding interaction with II amino acid residue and compounds 1, 3, 4, 5, 6 and 7 had in antimicrobial, anti-oxidant, and antimalarial properties similar to their standard drugs. Considering the outstanding pharmacological properties and their strict compliance with Lipinski’s rule, the synthesized 4-methylphenylsulphamoyl analogues could be considered as antimicrobial, antimalarial, and anti-oxidant drug candidates.

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