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COVID-19 is a global pandemic caused by infection with the SARS-CoV-2 virus. Remdesivir, a SARS-CoV-2 RNA polymerase inhibitor, is the only drug to have received widespread approval for treatment of COVID-19. The SARS-CoV-2 main protease enzyme (MPro), essential for viral replication and transcription, remains an active target in the search for new treatments. In this study, the ability of novel thiazolyl-indazole derivatives to inhibit MPro is evaluated. These compounds were synthesized via the heterocyclization of phenacyl bromide with (R)-carvone, (R)-pulegone and (R)-menthone thiosemicarbazones. The binding affinity and binding interactions of each compound were evaluated through Schrödinger Glide docking, AMBER molecular dynamics simulations, and MM-GBSA free energy estimation, and these results were compared with similar calculations of MPro binding various 5-mer substrates (VKLQA, VKLQS, VKLQG) and a previously identified MPro tight-binder X77. From these simulations, we can see that binding is driven by residue specific interactions such as π-stacking with His41, and S/π interactions with Met49 and Met165. The compounds were also experimentally evaluated in a MPro biochemical assay and the most potent compound containing a phenylthiazole moiety inhibited protease activity with an IC50 of 92.9 ​μM. This suggests that the phenylthiazole scaffold is a promising candidate for the development of future MPro inhibitors.

Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide–alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a–h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.

The new title 4-thiazolidinone derivative, C16H21N3O3S, was obtained from the cyclization reaction of 4-methyl-3-thiosemicarbazone and dimethyl acetylenedicarboxylate (DMAD). The cyclohexylidene ring has an envelope conformation with the stereogenic centre C atom as the flap. Its mean plane makes a dihedral angle of 56.23 (9)° with the thiazolidine ring mean plane. In the crystal, molecules are linked by C—H...O hydrogen bonds forming chains propagating in the [001] direction. Within the chains there are offset π–π interactions between the thiazolidine rings of inversion-related molecules [centroid–centroid distance = 3.703 (1) Å]. The chains are linked by further C—H...O hydrogen bonds, forming slabs parallel to the ac plane.

The title compound, C22H28O3, was prepared by a direct acetylation reaction of naturally occurring totarolenone. The molecule contains three fused rings, which exhibit different conformations. The central ring has a half-chair conformation, while the non-aromatic oxo-substituted ring has a screw-boat conformation. In the crystal, molecules are linked by C—H...O hydrogen bonds and C—H...π interactions, forming sheets parallel to the bc plane. The carbonyl O atoms and the C atom at the 6-position of the cyclohexene ring are each disordered over two sets of sites with major occupancy components of 0.63 (7) and 0.793 (14), respectively.

We have studied the inhibitory effect of some Monoterpenic Thiosemicarbazones on steel corrosion in 1 M HCl solution. The potentiodynamic polarization and electrochemical impedance spectroscopy were used. The Monoterpenic Thiosemicarbazones have inhibited significantly the dissolution of steel. The inhibition efficiency increased with increasing inhibitor concentration and also with the increase in temperature (293–323 K). Furthermore, the results obtained revealed that the adsorption of inhibitor on steel surface obeys Langmuir adsorption model and the thermodynamic parameters such as enthalpy and activation energy were determined. The scanning electron microscopy combined with dispersive X-ray spectroscopy examinations were used to see the shape of the surface morphology and to determine the elemental composition. Scanning electron microscope (SEM) images show that the surface damage decreases when the inhibitor is added. The quantum chemical calculations using density functional theory (DFT) were performed in order to provide some insights into the electronic density distribution as well as the nature of inhibitor-steel interaction.

There are two independent molecules (A and B) in the asymmetric unit of the title compound, C11H19N3S. In molecule B, two C atoms and the associated H atoms of the cyclohexene ring are disordered over two sets of sites with a site occupancy ratio of 0.649 (7):0.351 (7). The N—N—C—N fragments of the hydrazinecarbothioamide segments of both molecules are not planar, with a torsion angle of −5.8 (3)° for A and 11.6 (3)° for B. The stability of the conformations of both molecules is aided by the formation of intramolecular N—H...N hydrogen bonds. In the crystal, N—H...S hydrogen bonds link like molecules into R22(8) A + B dimers. These dimers are interconnected by additional N—H...S contacts, forming chains along the c-axis direction. The structure was refined as a two-component inversion twin.