Synthesis and characterization of ferrocene-based thiosemicarbazones along with their computational studies for potential as inhibitors for SARS-CoV-2

Abstract

Ferrocene and its derivatives are vital class of organometallic compounds having extensive biological activities. Six novel ferrocene-based thiosemicarbazones have been synthesized through the condensation reaction of acetyl ferrocene with differently substituted thiosemicarbazide. Furthermore, we used state-of-the-art computational docking approach to explore the theoretical aspects for possible antiviral potential of our synthesized compounds. All the six compounds were docked with M pro protein of SARS-CoV-2, which is very crucial protein for viral replication. Among the six derivatives, compounds 2 and 4 showed higher binding affinities with binding energy of − 6.7 and − 6.9 kcal/mol, respectively. The visualization of intermolecular interactions between synthesized derivatives and M pro protein illustrated that each of compounds 2 and 4 forms two hydrogen bonds accompanied by important hydrophobic interactions. The comparison of binding affinities with some recently approved drugs like remdesivir, chloroquine and hydroxychloroquine molecules are also made. The calculated binding energies of remdesivir, chloroquine and hydroxychloroquine molecules with M pro of COVID-19 was found to be − 7.00, − 5.20 and − 5.60 kcal/mol, respectively. The binding energy of compound 4 (− 6.9 kcal/mol) was almost equal to the remdesivir and greater than the binding energies of chloroquine and hydroxychloroquine. It is expected from the current investigation that our synthesized ferrocene-based thiosemicarbazones might have potential for drug against SARS-CoV-2.

Computational Drug Designing, Synthesis, Characterization and Anti-bacterial Activity Evaluation of Some Mixed Ligand–Metal Complexes of 2-hydroxybenzaldehydethiosemicarbazone as Primary Ligand

“…Transforming growth factor beta (Tgf-β) is onne of the cytokines involved in cell development, proliferation, and death [ 74 ]. The M pro is the primary protease enzyme of SARS-CoV-2 which is essential to the maturation and life cycle of the virus [ 75 ]. Blocking M pro might be a possible target for the disruption of the transcription and translation of the SARS-CoV-2 life cycle.…”

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…Among them, the best one was bisoctrizole . Additionally, some diaminobenzophenone derivatives, prototypical-ketoamide inhibitors, HIV protease inhibitors, leucoefdin, nutraceuticals, and others were also studied. ,,,,− Notably, Mohammad et al optimized some complexes of Mpro with ligands in the protein data bank (PDB) and rescored them by AutoDock Vina, with the best PDB structure being 6M2N.…”

Comprehensive Biological, Photodegradation, Density Functional Theory, and Docking Exploration of Zn(II) and Mn(II) complexes of Piroxicam

“…Metal complexes have therapeutic effects in diverse areas and are reported not only having anti‐inflammatory, antioxidant, and anti‐diabetic properties but also anti‐cancer properties [1,2] . Coordination chemistry plays an important role in establishing a wide variety of complexes to manage ligand kinetics up to optimum therapeutic potential with improved redox potential and therapeutic activities [3–7] . During tumorigenesis, the cells’ DNA divide uncontrollably which can be the main target for anti‐cancer drugs to lessen the proliferation of these cells [8–10] .…”

“…[1,2] Coordination chemistry plays an important role in establishing a wide variety of complexes to manage ligand kinetics up to optimum therapeutic potential with improved redox potential and therapeutic activities. [3][4][5][6][7] During tumorigenesis, the cells' DNA divide uncontrollably which can be the main target for anti-cancer drugs to lessen the proliferation of these cells. [8][9][10] Metals encapsulated between suitable ligands impart remarkable properties of DNA cleavage through binding with DNA's negative phosphate groups.…”