RESUMEN
In recent years, the viral outbreak named COVID-19 showed that infectious diseases have a huge impact on both global health and the financial and economic sectors. The lack of efficacious antiviral drugs worsened the health problem. Based on our previous experience, we investigated in vitro and in silico a series of quinoline-3-carboxylate derivatives against a SARS-CoV-2 isolate. In the present study, the in-vitro antiviral activity of a series of quinoline-3-carboxylate compounds and the in silico target-based molecular dynamics (MD) and metabolic studies are reported. The compounds' activity against SARS-CoV-2 was evaluated using plaque assay and RT-qPCR. Moreover, from the docking scores, it appears that the most active compounds (1j and 1o) exhibit stronger binding affinity to the primary viral protease (NSP5) and the exoribonuclease domain of non structural protein 14 (NSP14). Additionally, the in-silico metabolic analysis of 1j and 1o defines CYP2C9 and CYP3A4 as the major P450 enzymes involved in their metabolism.
RESUMEN
This review aims to provide a comprehensive report on the quinoline ring with respect to its synthesis, reactivity, and therapeutic values. The reactivity of quinoline for the metal, electrophile, and other reactive counterparts defines the shape of the quinoline pharmacophore, which is an important part of this report; moreover, its spectroscopic characteristics have been included herein with suitable illustration. The quinoline and its derivatives have been presented as well as the general synthetic approaches along with the new developments in the catalytic system; the relevant information is also summarized under the various separate activity classes. The synthesis of heterocyclic scaffolds has been a concern for scientists, so herein we have tried to include the synthetic parameters of quinoline with regard to the important pharmacological aspects.
