Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

Elizaveta V Panova; Julia K Voronina; Damir A Safin

doi:10.3390/ph16020286

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins

Pharmaceuticals (Basel). 2023 Feb 14;16(2):286. doi: 10.3390/ph16020286.

Authors

Elizaveta V Panova¹, Julia K Voronina², Damir A Safin^{1

3}

Affiliations

¹ Institute of Chemistry, University of Tyumen, Volodarskogo Str. 6, 625003 Tyumen, Russia.
² N.S. Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Leninsky Prospekt 31, GSP-1, 119991 Moscow, Russia.
³ Scientific and Educational and Innovation Center for Chemical and Pharmaceutical Technologies, Ural Federal University named after the First President of Russia B.N. Yeltsin, 620002 Ekaterinburg, Russia.

Abstract

We report two complexes [Cu(L^I)₂] (1) and [Cu(L^II)₂] (2) (HL^I = N-cyclohexyl-3-methoxysalicylideneimine, HL^II = N-cyclohexyl-3-ethoxysalicylideneimine). The ligands in both complexes are trans-1,5-N,O-coordinated, yielding a square planar CuN₂O₂ coordination core. The molecule of 1 is planar with two cyclohexyl groups oriented to the opposite sites of the planar part of a molecule, while the molecule of 2 is significantly bent with two cyclohexyl groups oriented to the same convex site of a molecule. It was established that both complexes in MeOH absorb in the UV region due to intraligand transitions and LMCT. Furthermore, the UV-vis spectra of both complexes revealed two low intense shoulders in the visible region at about 460 and 520 nm, which were attributed to d-d transitions. Both complexes were predicted to belong to a fourth class of toxicity with the negative BBB property and positive gastrointestinal absorption property. According to the molecular docking analysis results, both complexes are active against all the applied SARS-CoV-2 proteins with the best binding affinity with Nsp 14 (N7-MTase), PLpro and Mpro. The obtained docking scores of complexes are either comparable to or even higher than those of the initial ligands. Complex 1 was found to be more efficient upon interaction with the applied proteins in comparison to complex 2. Ligand efficiency scores for the initial ligands, 1 and 2 were also revealed.

Keywords: ADMET; COVID-19; SARS-CoV-2; Schiff base; X-ray; copper; crystal structure; molecular docking; molecular dynamics; synthesis.

Grants and funding

This research received no external funding.