Exploration of inhibitory action of Azo imidazole derivatives against COVID-19 main protease (Mpro): A computational study

<a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (Mpro) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (Mpros) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (Mpro) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a>

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Synthesis, characterization, and computational study of copper bipyridine complex [Cu (C18H24N2) (NO3)2] to explore its functional properties

Zeitschrift für Naturforschung C ◽

10.1515/znc-2021-0248 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Saleh S. Alarfaji ◽

Sajjad Hussain ◽

Abdullah G. Al-Sehemi ◽

Shabbir Muhammad ◽

Islam Ullah Khan ◽

...

Keyword(s):

Computational Study ◽

Coordination Complexes ◽

Mononuclear Complex ◽

Orthorhombic Space Group ◽

Main Protease ◽

Analysis Technique ◽

Infra Red ◽

Chemical Techniques ◽

The Stability ◽

Single Crystal Analysis

Abstract In the present study, copper (II) complex of 4, 4′-di-tert-butyl-2,2′-bipyridine [Cu (C18H24N2) (NO3)2], 1 is investigated through its synthesis and characterization using elemental analysis technique, infra-red spectroscopy, and single-crystal analysis. The compound 1 crystallizes in orthorhombic space group P212121. The copper atom in the mononuclear complex is hexa coordinated through two nitrogen and four oxygen atoms from bipyridine ligand and nitrate ligands. The thermal analysis depicts the stability of the entitled compound up to 170 °C, and the decomposition takes place in different steps between 170 and 1000 °C. Furthermore, quantum chemical techniques are used to study optoelectronic, nonlinear optical, and therapeutic bioactivity. The values of isotropic and anisotropic linear polarizabilities of compound 1 are calculated as 41.65 × 10−24 and 23.02 × 10−24 esu, respectively. Likewise, the static hyperpolarizability is calculated as 47.92 × 10−36 esu using M06 functional compared with para-nitroaniline (p-NA) and found several times larger than p-NA. Furthermore, the antiviral potential of compound 1 is studied using molecular docking technique where intermolecular interactions are checked between the entitled compound and two crucial proteins of SARS-CoV-2 (COVID-19). Our investigation indicated that compound 1 interacts more vigorously to spike protein than main protease (MPro) due to its better binding energy of −9.60 kcal/mol compared with −9.10 kcal/mol of MPro. Our current study anticipated that the above-entitled coordination complexes could be potential candidates for optoelectronic properties and their biological activity.

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Aldose Reductase Differential Inhibitors in Green Tea

Biomolecules ◽

10.3390/biom10071003 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1003 ◽

Cited By ~ 1

Author(s):

Francesco Balestri ◽

Giulio Poli ◽

Carlotta Pineschi ◽

Roberta Moschini ◽

Mario Cappiello ◽

...

Keyword(s):

Gallic Acid ◽

Green Tea ◽

Aldose Reductase ◽

Active Site ◽

Inhibitory Action ◽

Computational Study ◽

Epigallocatechin Gallate ◽

Polyol Pathway ◽

Differential Inhibition ◽

Tea Extract

Aldose reductase (AKR1B1), the first enzyme in the polyol pathway, is likely involved in the onset of diabetic complications. Differential inhibition of AKR1B1 has been proposed to counteract the damaging effects linked to the activity of the enzyme while preserving its detoxifying ability. Here, we show that epigallocatechin gallate (EGCG), one of the most representative catechins present in green tea, acts as a differential inhibitor of human recombinant AKR1B1. A kinetic analysis of EGCG, and of its components, gallic acid (GA) and epigallocatechin (EGC) as inhibitors of the reduction of L-idose, 4-hydroxy2,3-nonenal (HNE), and 3-glutathionyl l-4-dihydroxynonanal (GSHNE) revealed for the compounds a different model of inhibition toward the different substrates. While EGCG preferentially inhibited L-idose and GSHNE reduction with respect to HNE, gallic acid, which was still active in inhibiting the reduction of the sugar, was less active in inhibiting HNE and GSHNE reduction. EGC was found to be less efficient as an inhibitor of AKR1B1 and devoid of any differential inhibitory action. A computational study defined different interactive modes for the three substrates on the AKR1B1 active site and suggested a rationale for the observed differential inhibition. A chromatographic fractionation of an alcoholic green tea extract revealed that, besides EGCG and GA, other components may exhibit the differential inhibition of AKR1B1.

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Naturally occurring anthraquinones as potential inhibitors of SARS-CoV-2 main protease: an integrated computational study

Biologia ◽

10.1007/s11756-021-01004-4 ◽

2022 ◽

Author(s):

Sourav Das ◽

Anirudh Singh ◽

Sintu Kumar Samanta ◽

Atanu Singha Roy

Keyword(s):

Computational Study ◽

Naturally Occurring ◽

Main Protease ◽

Potential Inhibitors

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Inhibition of Cortical Neurones by Imidazole and Some Derivatives

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y73-122 ◽

1973 ◽

Vol 51 (11) ◽

pp. 790-797 ◽

Cited By ~ 37

Author(s):

J. M. Godfraind ◽

K. Krnjević ◽

H. Maretić ◽

R. Pumain

Keyword(s):

Cyclic Amp ◽

Cyclic Nucleotide ◽

Inhibitory Action ◽

Aminobutyric Acid ◽

Phosphodiesterase Activity ◽

Inhibitory Potency ◽

Imidazole Derivatives ◽

Propyl Esters ◽

Relative Potencies ◽

Acetic Acids

Systematic tests of imidazole and 15 derivatives, applied by microiontophoresis in anesthetized cats, showed a high inhibitory potency of imidazole-4-acetic and imidazole-4-propionic acids and also of their amyl and propyl esters; but imidazole 4-carboxylic and 1-methylimidazole-4-acetic acids were largely inactive. This order of potency is very different from the relative potencies of imidazole derivatives in facilitating cyclic nucleotide phosphodiesterase activity. It is therefore unlikely that their inhibitory action is simply related to changes in cellular levels of cyclic AMP. The characteristics of this action, including lack of antagonism by bicuculline, are consistent with the possibility that it is mediated by γ-aminobutyric acid receptors.

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