Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro).

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the L-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1H NMR, 13C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (Mpro) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2.

Molecular Iodine-Catalyzed Synthesis of Imidazo[1,2-a]Pyridines: Screening of Their In Silico Selectivity, Binding Affinity to Biological Targets, and Density Functional Theory Studies Insight.

The present paper discloses an ultrasonication strategy assisted by molecular iodine as an environmentally benign catalyst leading to the synthesis of pharmacologically significant imidazo[1,2-a]pyridine scaffolds. The molecular-iodine-catalyzed approach for the synthesis of biologically active synthetic equivalents was achieved through three-component coupling embracing 2-aminopyridine derivatives, pertinent acetophenones, and dimedone in water medium under aerobic conditions. The higher product yield (up to 96%) with a miniature reaction time and modest catalyst loading as demonstrated by higher ecological compatibility and sustainability factors are fascinating features of this protocol. The structures of synthesized compounds were accomplished through FT-IR, 1H NMR,13C NMR, mass, and elemental analysis data. The virtual screening of synthetic moieties was performed to ascertain the in silico selectivity and binding affinities against several biological targets. Lipinski's rules of five, ADMET, and TOPKAT descriptors were used to evaluate the drug-likeness assets. Furthermore, a quantum computational study was computed at the B3LYP/6-311G++(d,p) level of theory to investigate the density functional theory-based chemical reactivity parameters and HOMO-LUMO energy gap of the synthesized derivatives. The present studies open the way for in vitro and in vivo testing of synthesized derivatives as potent inhibitors with an improved pharmacological profile against farnesyl diphosphate synthase, phosphodiesterase III, CXCR4, and GABAa receptor agonists.

Hydromagnesite sheets impregnated with cobalt-ferrite magnetic nanoparticles as heterogeneous catalytic system for the synthesis of imidazo[1,2-a]pyridine scaffolds.

This paper manifests an A3-coupling strategy assisted by novel hydromagnesite sheets impregnated with cobalt ferrite (CoFe2O4-HMS) magnetic nanoparticles (MNPs) as an environmentally benign nanocomposite to synthesize imidazo[1,2-a]pyridine scaffolds under ultrasonication. The synthesis of these biologically active derivatives was achieved through A3-coupling employing 2-aminopyridines derivatives, pertinent aryl aldehydes, and phenylacetylene in the presence of polyethylene glycol 400 (PEG 400) as a green solvent under aerobic conditions. Based on its high product yield (up to 94%) in a short reaction time, with a modest catalyst loading, excellent catalyst, and solvent recyclability without substantial loss of operation (up to five synthetic cycles), as demonstrated by the high ecological compatibility and sustainability factors, this strategy follows the principles of green chemistry. The synthesized nanocomposite was characterized via several spectroanalytical techniques, including PXRD, FE-SEM, HR-TEM, EDAX, ICP-AES, FT-IR, Raman spectroscopy, CO2-TPD, TGA-DTA-DTG analyses, magnetic studies, and nitrogen porosimetry. Furthermore, the structures of synthesized compounds were confirmed based on FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis data.