Discovery of novel thioquinazoline--aryl-acetamide/-arylacetohydrazide hybrids as anti-SARS-CoV-2 agents: Synthesis, biological evaluation, and molecular docking studies.

In the current investigation, two novel series of (tetrahydro)thioquinazoline--arylacetamides and (tetrahydro)thioquinazoline--arylacetohydrazides were designed, synthesized and investigated for their antiviral activity against SARS-CoV-2. The thioquinazoline--arylacetamide as well as the tetrahydrothioquinazoline--arylacetohydrazides and showed potent antiviral activity with IC of 21.4, 38.45 and 26.4 µM, respectively. In addition, and demonstrated potential selectivity toward the SARS-CoV-2 over the host cells with of 10.67 and 16.04, respectively. Further evaluation of the mechanism of action of the three derivatives , and displayed that they can inhibit the virus at the adsorption as well as at the replication stages, in addition to their virucidal properties. In addition, , and demonstrated satisfactory physicochemical properties as well as drug-likeness properties to be further optimized for the discovery of novel antiviral agents. The docking simulation on M binding site predicted the binding pattern of the target compounds rationalizing their differential activity based on their hydrophobic interaction and fitting in the hydrophobic S2 subsite of the binding site.