Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the effective combination therapy as pharmaceutical drug. The antimicrobial activity was investigated using molecular docking. The investigated molecule demonstrated a high affinity for binding within the active sites of antibacterial and antimalarial proteins. The high affinity of the antibacterial protein was proved by its low binding energy (−7.97 kcal/mol) and a low inhibition constant value (1.43 µM). The formation of four conventional hydrogen bonds in ligand–protein interactions confirmed the high stability of the resulting complexes. When compared to known standard drugs, the studied molecule displayed a remarkable antimalarial activity, as indicated by higher binding affinity (B.E. −5.86 kcal/mol & Ki = 50.23 M). The pre-selected molecule could be presented as a promising drug candidate for the development of novel antimicrobial agents.

Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 M^pro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6–311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from −8.19 to −7.33 Kcal/mol for 4c and 4a to −6.10 to −6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good M^pro inhibitors. Moreover, the drug-likeness studies, including Lipinski’s rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.

This paper explores a dual inhibition of main protease (Mpro) and nonstructural protein 10/nonstructural protein 16 (NSP16) methyltransferase complex as the key targets for COVID-19 therapy. These are based on the new Schiff-base ligand that was obtained from the condensation of (4-chloro-3-methyl phenyl) hydrazine with 2-pyridine-carboxaldehyde and its novel Schiff-base metal complexes. These include Ni(II), Pd(II), Pt(II), Zn(II), and Hg(II). The newly synthesized compounds have been characterized using FT-IR, ¹H NMR, ¹³C NMR, and elemental analysis. The results suggested that the Schiff-base ligand is coordinated as a bidentate ligand through the nitrogen atoms of the azomethine group and pyridyl ring. In addition, the biological activity of the prepared complexes was examined against Pseudomonas aeruginosa and Staphylococcus aureus, and the results showed that the Zn(II) complex has the highest activity compared with other compounds. The active sites were found by looking at the molecular electrostatic potential (MEP) maps of the above ligands and complexes. The activity of the compound and its Ni(II) and Zn(II) complexes against Mpro and NSP10/ NSP16 was investigated using a molecular docking approach. They showed excellent binding energies ranging from −5.9 to −7.2 kcal/mol and −5.8 to −7.2 for Mpro and NSP16, respectively. All conformers of the metal complexes were docked with the active site of the NSP16 receptor, showing a binding affinity of 100%. According to our knowledge, this was the first report of these metal complexes as dual inhibitors for Mpro and NSP16 of SARS-CoV-2.