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, viz., 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 (Mpro) 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 Mpro 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.

Multicomponent synthesis of pyrrolo[2,1-a]isoindolylidene-malononitrile (PIYM) fluorophores and their photophysical properties.

From the array of small molecule organic fluorophores available as functional materials and in biology, synthetic procedures that allow for a simpler and rapid synthesis of organic fluorophores with desirable photophysical properties are in high demand. In addition, fluorophores with good brightness and tuneability in both solid and solution states are only available in certain numbers. Herein, we introduce a new family of pyrrolo[2,1-a]isoindolylidene-malononitrile (PIYM) fluorophores that exhibit pronounced emission in the visible region in solution and red-NIR emission in the solid state, with tuneability, efficient brightness and stability. PIYM fluorophores were efficiently synthesized via two simple MCR reaction pathways from commercially available, as well as newly synthesized, building blocks. Furthermore, the observed photophysical nature is rationalized from both electrochemical and theoretical calculations (DFT and TD-DFT). In the future, we anticipate that these PIYM fluorophores, with their excellent stability and lower molecular weight, will open ways to enhance the development of NIR-emitting fluorophores with more significant applications in both materials and biological fields.