Green and Regioselective Approach for the Synthesis of 3-Substituted Indole Based 1,2-Dihydropyridine and Azaxanthone Derivatives as a Potential Lead for SARS-CoV-2 and Delta Plus Mutant Virus: DFT and Docking Studies.

Great attempts have been done for the development of novel antiviral compounds against SAR-CoV-2 to end this pandemic situation and save human society. Herewith, we have synthesized 3-substituted indole/2-substituted pyrrole 1,2-dihydropyridine and azaxanthone scaffolds using simple, commercially available starting materials in a one-pot, green, and regioselective manner. Further, the regioselectivity of product formation was confirmed by various studies such as controlled experiments, density functional theory (DFT), Mulliken atomic charge, and electrostatic potential (ESP) surface. In addition, 3-substituted indole 1,2-dihydropyridine was successfully converted into a biologically enriched pharmacophore scaffold, ., indolylimidazopyridinylbenzofuran scaffold, in excellent yield. Moreover, the synthesized 3-substituted indole 1,2-dihydropyridine/2-substituted pyrroles were analyzed in docking studies for anti-SARS-CoV-2 properties against their main protease (M) and anti-Delta plus properties against their protein of the Delta plus K417N mutant. Further, the drug-likeness prediction was analyzed by the Lipinski rule and other pharmacokinetic properties like absorption, distribution, metabolism, excretion, and toxicity using preADMET prediction. Interestingly, the docking results show that out of 20 synthesized compounds, 5 of them for M of SAR-CoV-2 and 9 of them for 7NX7 spike glycoprotein's A chain of Delta plus K417N show greater binding affinity when compared with remdesivir that is the first to receive FDA approval and is currently used as a potent drug for the treatment of COVID-19. These results suggest that indole/pyrrole substituted 1,2-dihydropyridine derivatives are capable of combating SARS-CoV-2 and its Delta plus mutant.