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A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best in-silico complexation affinities were synthesized, and their In-vitro cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated in-silico. For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it via spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively. Communicated by Ramaswamy H. Sarma

A series of novel 2-iminothiazolidin-4-one analogs have been synthesized from limonaketone, and structurally characterized by HR-MS

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 and (R)-pulegone thiosemicarbazones. The binding affinity and atomistic 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). 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.

The present work focuses on the synthesis, structural characterization and electrochemical investigation of some heterocyclic compounds prepared from d -limonene. Firstly, 3-acetylisoxazoline was synthesized from d -limonene, this precursor is then converted to its thiosemicarbazone derivatives which were then cyclized to produce their corresponding thiazolidine-4-ones. The obtained compounds were characterized by FT-IR, 1H NMR, 13C NMR and mass spectrometric techniques. Further, DFT quantum chemical studies were also used to interpret the structural properties of the compounds using the B3LYP/6–311++G (d, p) basis set. The obtained results from experimental and theoretical studies were in good agreement showing that compounds bearing both isoxazoline and thiazolidine-4-one moieties act as good corrosion inhibitors for stainless steel in 1 M sulfuric acid.

Treatment of thiosemicarbazones prepared from sesquiterpenes with ethyl 2-bromoacetate in the presence of sodium acetate afforded the corresponding thiazolidin-4-ones. The structures of all the newly synthesized compounds were established by considering spectral and single-crystal X-ray diffraction data. The title compound, ethyl 2-((Z)-2-{(Z)-[(1aR,5aR,9aS)-1,1-dichloro-1a,5,5,7-tetramethyl-1a,2,3,4,5,5a,8,9-octahydro-1H-benzo[a]cyclopropa[b][7]annulen-8-ylidene]hydrazono}-4-oxothiazolidin-3-yl)acetate, C

The title compound, (4bS,8aR)-1-isopropyl-4 b,8,8-trimethyl-7-oxo-4 b,7,8,8a,9,10-hexa­hydro­phenanthren-2-yl acetate, was prepared by a direct acetyl­ation reaction of naturally occurring totarolenone. In the crystal, mol­ecules are linked to each other by C—H⋯O hydrogen bonds and C—H⋯π inter­actions, forming sheets parallel to the bc 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.

The title compounds C11H16Cl2O3 (III) and C11H16Br2O3 (IV) have been prepared from (S)-Limonen. Their crystal structure and absolute configuration have been determined by X-ray analysis which confirmed the 1′S absolute configuration at the cyclopropyl moiety, in agreement with the known absolute configuration of the starting material. Both (III) and (IV) are orthorhombic, space group P212121 with a = 7.2558(4) A (for III) 7.4058(6) A (for IV), b = 9.7885(5) A (for III) 9.7459(7) A (for IV), c = 17.7551(10) A (for III) 18.0354(14) A (for IV), α = 90°, β = 90°, γ = 90° and Z = 4. Absolute configuration determination, via an X-ray crystallographic study, of two optically active cyclopropyl-ketoacids.

Herein we report an efficient one pot synthesis of new chiral 4,5-dihydro-4-arylspiro[1,3,4-thiadiazole]-5,2′-camphane-2-carboxylic acid ethyl esters 5–7 and 4,5-dihydro-3-arylspiro[1,4,2-oxathiazole]-5,2′-camphane 11–13, using 1,3-dipolar cycloaddition of nitrilimines 2–4 and nitrile oxides 8–10 to (1R)-thiocamphor 1 respectively. The structure of the newly prepared 1,3,4-thiadiazoles 5–7 (obtained as pure diastereoisomers) were fully established via spectroscopic analysis and X-ray structural analysis which proved the absolute configuration of the C5 spiranic carbon to be (R). NMR spectral analysis were also very useful to show the new 1,4,2-oxathiazoles 11–13 are mixtures of two (5R)/(5S) diastereoisomers with the ratio 6:4,7:3 and 6:4 respectively.