Water‐SDS‐Ionic Liquid Catalytic System for the Synthesis of Pyrano‐chromenes and in‐silicio Approach to Predict Inhibitory Activity Against Mpro of SARS‐CoV‐2

A simple, efficient and rapid one pot green synthesis of pyrano‐chromene derivatives have been realized by using water‐SDS‐neutral ionic liquid ([BMIm]Br) miceller system via sequential addition of aromatic aldehyde, malonitrile (Knoevenagel condensation) followed by 4‐hydroxy coumarin. In all cases the obtained products were produced well to excellent yields. This protocol shifts a versatile solvent‐catalyst system, which has many advantages such as eco‐friendly condition, simple workup and reuse (recycle) of post reaction waste containing sodium dodecyl sulphate and ionic liquid without loss of catalytic activity. The efficacy of the synthesised compounds as inhibitors of the SARS‐CoV‐2 main protease (Mpro) was investigated through molecular docking studies. Our study showed that most of the synthetic compounds exhibited excellent capability to block the SARS‐CoV‐2 Mpro by binding with crucial amino acid residues in catalytic pockets, compared to naturally occurring known SARS‐CoV‐2 Mpro inhibitors, flavonoids like Baicalein, Quercetin, and Quercetagetin. [ FROM AUTHOR]

Design, synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor.

PURPOSE: Vortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2. METHODS: In this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper. RESULTS: Based on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine. CONCLUSION: This study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.

Bis-indolylation of aldehydes and ketones using silica-supported FeCl3: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites.

We report herein an operationally simple, efficient and versatile procedure for the synthesis of bis-indolylmethanes via the reaction of indoles with aldehydes or ketones in the presence of silica-supported ferric chloride under grindstone conditions. The prepared supported catalyst was characterized by SEM and EDX spectroscopy. The present protocol has several advantages such as shorter reaction time, high yield, avoidance of using harmful organic solvents during the reaction and tolerance of a wide range of functional groups. Molecular docking studies targeted toward the binding site of SARS-CoV-2 main protease (3CLpro or Mpro) enzymes were investigated with the synthesized bis-indoles. Our study revealed that some of the synthesized compounds have potentiality to inhibit the SARS-CoV-2 Mpro enzyme by interacting with key amino acid residues of the active sites via hydrophobic as well as hydrogen bonding interactions.