A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins.

UNLABELLED

Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2-chromen-2-one (), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4-1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2-chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, H, and C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of . ADMET properties of were evaluated using the respective online tools. It was established that exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of with the applied proteins was also studied using molecular dynamics simulations.

GRAPHICAL ABSTRACT

A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one () is reported. The structure and electronic properties of were examined by the DFT calculations. ADMET properties of were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of with a series of the SARS-CoV-2 proteins.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s12039-022-02127-0.