Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives

Bioorg Med Chem Lett. 2024 Feb 27:129679. doi: 10.1016/j.bmcl.2024.129679. Online ahead of print.ABSTRACTSeven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with 2-, 3-, 4-, 5-, 6-, and 8-quinoline carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 Mpro enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2 Mpro with IC50 values ranging from 16 to 44 μM. Additionally, all of the derivatives showed strong interaction with the SARS-CoV-2 Mpro substrate binding pocket, with docking energy scores ranging from -8.0 to -8.5 kcal/mol. These values are comparable to that of N3 peptide (8.1 kcal/mol) and more favorable than GC-373 (-7.6 kcal/mol) and ML-188 (-7.5 kcal/mol), all of which are known SARS-CoV-2 Mpro inhibitors. Furthermore, in silico absorption, distribution, metabolism, and elimination (ADME) profiles indicate that the derivatives have good drug-likeness properties. Overall, this study highlights the potential of the furanochromene-quinoline hydrazone scaffold as a SARS-CoV-2 Mpro inhibitor.PMID:38423371 | DOI:10.1016/j.bmcl.2024.129679

Source: Bioorganic and Medicinal Chemistry Letters - February 29, 2024 Category: Chemistry Authors: Blake M Shellenberger Olivia N Basile Joel Cassel Morgan R Olsen Joseph M Salvino Luis J Montaner Ian Tietjen Geneive E Henry Source Type: research