C 16H21NO5S, triclinic, P1 (no. 2), a = 7.3395(9) Å, b = 11.103(1) Å, c = 11.391(1) Å, a = 107.933(9)°, b = 95.12(1)°, g = 99.96(1)°, V = 859.8 Å 3 , Z = 2, R gt(F) = 0.062, wRref(F 2 ) = 0.218, T = 293 K. Source of materialFirstly, the 4-tert-butyl-2-(4-nitrophenylsulfanyl)cyclohexanone was obtained from the reaction of 2-bromo-4-tert-butyl-cyclohexanone and 4-nitrobenzenethiol [1], then to a solution of the product (2.0 g, 6.5 mmol) in methanol (10 mL) and CH2Cl2 (3 mL) at 273 K was added slowly a solution of hydrogen peroxide (30 %, 3.7 mL, 32.5 mmol) and selenium dioxide (0.72 g, 6.5 mmol) in methanol [2]. After stirring for 5 h, a saturated aqueous NaCl solution (40 mL) was added and the crude product was extracted with CH2Cl2 (3 × 30 mL). The organic layer was dried over anhydrous MgSO4. The solvent was removed and the amorphous yellow solid was recrystallized from ethanol giving 1.61 g of the title compound (4.74 mmol, 72 % yield, m.p. 405-406 K). Crystals were obtained by slow evaporation from anhydrous ethanol at 298 K. Elemental analysis: found C, 56.23 %; H, 6.03 %; N, 3.99 %; calc. for C16H21NO5S C, 56.62 %; H, 6.24 %; N, 4.13 %. Experimental detailsThe high Uii values for C14 C16 can be ascribed to the rotational disorder of the tert-butyl group. DiscussionThe cyclohexanone ring is in a slightly distorted chair conformation, the Cremer and Poples ring-puckering [3] parameters being: q2 = 0.0715 (6)

Os estudos cristalográficos mostram que o poliedro de coordenação ao redor do átomo de Te, em cada um dos compostos (p-tol)Te[C(H)=C(Cl)Ph]X 2 , com X = Cl (1), Br (2) e I (3), é uma Ψ-bipirâmide pentagonal distorcida. O grupo vinil em (1) adota uma configuração E o que impede a formação de uma interação intramolecular Te … Cl e em seu lugar é encontrada uma interação intramolecular Te … p. O poliedro de coordenação é formado por um arranjo linear Cl-Te-Cl com o plano pentagonal definido por dois átomos de C dos substituintes orgânicos, um contato intermolecular Te … Cl, uma interação Te … p e um par isolado de elétrons estereoquimicamente ativo. Geometrias de coordenação semelhantes são encontradas para as estruturas com X = Br (2) e I (3), mas a interação p é substituída por uma interação intramolecular Te … Cl devido à adoção de uma configuração Z em torno da ligação vinil. As diferenças nas estruturas são facilmente explicadas em termos de efeitos eletrônicos. Estudos de docking em catepsina B com (1')-(3'), ou seja, compostos 1 a 3 em que há um haleto a menos ligado ao átomo de Te, mostram que há uma ligação eficiente com a proteína pela formação da ligação covalente Te-S Cys29 com a estabilização proporcionada por uma combinação de interações N-H … p, C-H … p e Cl vinyl … H. Estes resultados são comparáveis aos obtidos com inibidores conhecidos da catepsina B o que sugere que os compostos estudados têm potencial atividade biológica.Crystallography shows that the Te atom in each of (p-tol)Te[C(H)=C(Cl)Ph]X 2 , for X = Cl (1), Br (2) and I (3), is within a distorted Ψ-pentagonal bipyramidal geometry. An E configuration for the vinyl group in (1) precludes the formation of an intramolecular Te … Cl interaction so that an intramolecular Te … p interaction is found instead. The coordination environment features a linear Cl-Te-Cl arrangement with the pentagonal plane defined by the two C atoms of the organic substituents, an intermolecular Te … Cl contact, a Te … p interaction and a stereochemically active lone pair of electrons. In the X = Br (2) and I (3) structures, similar coordination geometries are found but the Te … p contact is replaced by an intramolecular Te … Cl contact owing to the adoption of a Z configuration about the vinyl bond. The differences in structure are readily explained in terms of electronic effects. Docking studies of cathepsin B with (1')-(3'), i.e. 1-3 less one Te-bound halide, show efficient binding through the agency of covalent Te-S Cys29 bonds with stabilization afforded by a combination of N-H … p, C-H … p and Cl vinyl … H interactions. These results comparable favorably with known inhibitors of cathepsin B suggesting the title compounds have potential biological activity.Keywords: organotellurium-dihalides, docking studies, cathepsin B, crystal structures, supramolecular arrangements 2-Chlorovinyl Tellurium Dihalides, (p-tol)Te[C(H)=C(Cl)Ph]X 2 for X = Cl, Br and I J. Braz. Chem. Soc. 2156 IntroductionOrganotellurium halides comprise an interesting class of compounds owing...

Inhibition of cyclin dependent kinases (CDKs) 4 and 6 prevent cells from entering the synthesis phase of the cell cycle. CDK4 and 6 are therefore important drug targets in various cancers. The selective CDK4/6 inhibitor palbociclib is approved for the treatment of breast cancer and has shown activity in a cellular model of mixed lineage leukaemia (MLL)‐rearranged acute myeloid leukaemia (AML). We studied the interactions of palbociclib and CDK6 using molecular dynamics simulations. Analysis of the simulations suggested several interactions that stabilized the drug in its binding site and that were not observed in the crystal structure of the protein‐drug complex. These included a hydrogen bond to His 100 that was hitherto not reported and several hydrophobic contacts. Evolutionary‐based bioinformatic analysis was used to suggest two mutants, D163G and H100L that would potentially yield drug resistance, as they lead to loss of important protein–drug interactions without hindering the viability of the protein. One of the mutants involved a change in the glycine of the well‐conserved DFG motif of the kinase. Interestingly, CDK6‐dependent human AML cells stably expressing either mutant retained sensitivity to palbociclib, indicating that the protein‐drug interactions are not affected by these. Furthermore, the cells were proliferative in the absence of palbociclib, indicating that the Asp to Gly mutation in the DFG motif did not interfere with the catalytic activity of the protein.

The title meroterpene preaustinoid A (systematic name: methyl 15-hydr­oxy-2,6,6,10,13,15-hexa­methyl-17-methyl­ene-7,14,16-trioxotetra­cyclo­[11.3.1.02,11.05,10]hepta­decane-1-car­box­yl­ate), C26H36O6, features a fused four-ring arrangement. Three rings are in different distorted chair conformations and the other is in a distorted boat conformation. The absolute configuration was established based on [αD] = −4.97° (c = 1.10 g l−1, CH2Cl2). In the crystal, the mol­ecules are connected into supra­molecular chains via O—H⋯O hydrogen bonds.

Cathepsins L (catL) and B play an important role in tumor progression and have been considered promising therapeutic targets in the development of novel anticancer agents. Using a bioactivity-guided fractionation, a series of triterpenoids was identified as a new class of competitive inhibitors towards cathepsin L with affinity values in micromolar range. Among the 14 compounds evaluated, the most promising were 3-epiursolic acid (3), 3-(hydroxyimino)oleanolic acid (9), and 3-(hydroxyimino)masticadienoic acid (13) with IC50 values of 6.5, 2.4, and 2.6 μM on catL, respectively. Most of the evaluated triterpenoids do not inhibit cathepsin B. Thus, the evaluated compounds exhibit a great potential to help in the design of new inhibitors with enhanced potency and affinity towards catL. Docking studies were performed in order to gain insight on the binding mode and SAR of these compounds.

Abstract. The molecular structures of the halotelluroxetanes pMeOC6H4Te(X)[C(=C(H)Xꞌ)C(CH2)nO], X = Xꞌ = Cl and n = 6 (1) and X = Cl, Xꞌ = Br and n = 5 (4), show similar binuclear aggregates sustained by { … Te-O}2 cores comprising covalent Te-O and secondary Te⋯O interactions. The resulting C2ClO2(lone-pair) sets define pseudo-octahedral geometries. In each structure, C-X⋯(arene) interactions lead to supramolecular layers. Literature studies have shown these and related compounds (i.e. 2: X = Xꞌ = Cl and n = 5; 3: X = Xꞌ = Br and n = 5) to inhibit Cathepsins B, K, L and S to varying extents. Molecular docking calculations have been conducted on ligands (i.e. cations derived by removal of the telluriumbound X atoms) 1ꞌ-3ꞌ (note 3ꞌ = 4ꞌ) enabling correlations between affinity for sub-sites and inhibition. The common feature of all docked complexes was the formation of a Te-S covalent bond with cysteine residues, the relative stability of the ligands with an E-configuration and the formation of a C-O … π interaction with the phenyl ring; for 1ꞌ the Te-S covalent bond was weak, a result correlating with its low inhibition profile. At the next level differences are apparent, especially with respect to the interactions formed by the organic-ligand-bound halides.

In the title compound, C17H15NO4, the conformation about the C=C double bond [1.348 (2) Å] is E with the ketone group almost co-planar [C—C—C—C torsion angle = 7.2 (2)°] but the phenyl group twisted away [C—C—C—C = 160.93 (17)°]. The terminal aromatic rings are almost perpendicular to each other [dihedral angle = 81.61 (9)°] giving the mol­ecule an overall U-shape. The crystal packing feature benzene-C—H⋯O(ketone) contacts that lead to supra­molecular helical chains along the b axis. These are connected by π–π inter­actions between benzene and phenyl rings [inter-centroid distance = 3.6648 (14) Å], resulting in the formation of a supra­molecular layer in the bc plane.

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