In vitro and in silico study of the biological activity of manganese(III) inverse-[9-MC-3]-metallacrowns and manganese(II) complexes with the anti-inflammatory drugs diclofenac or indomethacin

Succinic acid and its derivatives have many important uses, especially in pharmaceutical and polymer industry. The 2-(substituted benzylidene)succinic acids also known as substituted phenylitaconic acids are utilized in the synthesis of some lignans, lignanamides and renin inhibitors. In view of this, the present in-silico study aimed to calculate the molecular properties, bioactivity score and toxicity of several benzylidenesuccinic acids as well as some selected anti-inflammatory drugs by computational methods. The study revealed that all the compounds obeyed Lipinski’s rule of five, indicating drug likeness properties. The bioactivity data revealed that the 2-(substituted benzylidene)succinic acids were active as Nuclear receptor ligands, Enzyme inhibitors, GPCR ligands and Ion channel modulators. Among all, 2-(3,5-di-tert-butyl-4-hydroxybenzylidene)succinic acid was predicted as non-toxic with better in-silico molecular properties and bioactivity as Nuclear receptor ligand, Enzyme inhibitor, GPCR ligand, Ion channel modulator and Protease inhibitor compared to some of the predicted anti-inflammatory drugs.

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In silico study: Assessment of the inhibition of cyclo-oxygenase 2 by ibuprofen by validating molecular docking and cardiovascular effects reported during the COVID 19 pandemic

International Journal of Pharma Sciences and Research ◽

10.21817/ijpsr/2020/v11i10/201110009 ◽

2020 ◽

Vol 11 (10) ◽

pp. 232-239

Author(s):

Hamza Nadjib Merad-boudia ◽

Majda Dali-Sahi ◽

Baya Guermouche ◽

Nouria Dennoun-Medjati

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Targets ◽

3D Structure ◽

Cardiovascular Effects ◽

Crystallographic Structure ◽

Discovery Studio ◽

In Silico Study ◽

Inflammatory Drugs ◽

Anti Inflammatory

Introduction The Covid 19 pandemic has put the cardiovascular risk incurred when using nonsteroidal anti-inflammatory drugs at the heart of the discussion. Based on the information currently available, WHO does not recommend the use of ibuprofen. the objective is to evaluate the inhibition of cyclo-oxygenase 2 by ibuprofen by validating molecular docking. Method The crystallographic structure of ibuprofen bound to cyclooxygenase-2 was obtained from the Protein Data Bank (PDB) at a resolution <3.00 Å. The receiver was visualized using Discovery Studio Visualizer version 2.5.5. It was efficiently prepared using AutoDock / Vina software. The 3D structure of Ligand (Ibuprofen) was downloaded from the Drugbak database (https://www.drugbank.ca/): Accession number DB01050 Results Molecular docking was chosen as the first-line discrimination of the ibuprofen-COX2 intercation for the in silico study of putative competitors. The complex formed by Ibuprofen-COX 2 from the experimental model gives a docking score (Affinity: -7.3 (kcal / mol) with a mean square deviation of (RMSD = 23.884). Conclusion The evaluation of the inhibition of cyclo-oxygenase 2 by ibuprofen was validated by molecular docking. Cardiovascular effects already reported in patients treated with traditional non-steroidal anti-inflammatory drugs and coxibs have been observed in patients with COVID 19. Molecular docking becomes an essential step in drug discovery to explore other drug targets

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