What is it about?
This manuscript reports the synthesis of seven new antioxidant agents based on the combination of thiazole, pyridine, triazole and pyrazole moieties. The reported seven compounds (1-7) were obtained via the condensation between thiazole and pyridine derivatives amines with hy-droxymethylpyrazole derivatives and hydroxymethyltriazole to obtain new heterocyclic com-pounds with good yields up to 89%, then we studied their antioxidant activity using DPPH re-duction method where we have the best result of radical scavenging is IC50=13.05 ± 3.73 µg/ml for the ligand (1). These experimentally results were well correlated with theoretical ones re-vealed by DFT where the ligand (1) has the highest value of EHOMO and lowest value of ELUMO, with two bonds in the active site of APX with the amino acids Ala167 and Arg172 compared to the ascorbic acid that has a bond with the same amino acid (Ala167). Docking results shows also a good correlation between experience and theory with α-cyclodextrin as best drug delivery system (better binding affinity than caffeic acid).
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Why is it important?
- Seven mono-alkylated compounds were prepared and characterized using FTIR, 1H and 13C NMR. - The studied compounds were tested for their antioxidant activity using DPPH assay. - All the compounds were investigated using DFT in gas and methanol phase. - The compound (1) has the best affinity with Ascorbate peroxidase (Biological target). - α-cyclodextrin is the best drug delivery system with the best binding affinities of the studied compounds than Caffeic acid.
Perspectives
Seven ligands fusing two different heterocyclic compounds (A and B-rings) were prepared in same reaction protocol to give good yields up to 89.85%. The ligand (1) gives the best results with IC50= 13.05 µg/ml due to the presence of proton NH to give to DPPH radical with a conju-gation in the A-ring. The three quantum descriptors give us some indications with the highest value of it for (1): EHOMO = 5.5870 eV and with the lowest value of ELUMO=0.0598 eV it’s either electron donor and acceptor, and the higher value of this quantum descriptor which is Egap = 5.6468 eV in gas phase and Egap = 5.562 eV in liquid phase (Methanol), so it has higher stability compared to the standard (ascorbic acid) with 5.5299eV and 5.4395 eV respectively with no changes of the compounds bonds and angles change in neutral or methanol phases but this last boost the hydrogen transfer. Furthermore, the docking results shows that the ligand (1) has an inverse interaction with the Ala 167 by accepting a proton from the amino acid instead of the Ascorbic acid who is giving to the same amino acid a proton from C10, also the ligand (1) is the only ligand who interact with the amino acid Ala 167 with the higher value of rmsd = 1.9744 between the ligands who have interactions with the active site ligands (3), (5) and (7)) so all this make it the best candidate as an antioxidant which is confirmed by the experimental studies. For the drug delivery study, The ACD is best system for all the compounds due to the smallest cavi-ty size which makes the binding affinities favorable and possible to prepare prospective nano-antioxidants.
Rachid Touzani
University Mohammed Premier, Oujda, Morocco
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This page is a summary of: New heterocyclic compounds: synthesis, antioxidant activity and computational insights of nano-antioxidant as ascorbate peroxidase inhibitor by various cyclodextrin as drug delivery systems, Current Drug Delivery, October 2020, Bentham Science Publishers,
DOI: 10.2174/1567201817999201001205627.
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