Synthesis, crystal structure and Hirshfeld surface analysis of 2-({5-[(naphthalen-1-yl)meth-yl]-4-phenyl-4H-1,2,4-triazol-3-yl}sulfan-yl)-1-(4-nitro-phen-yl)ethanone.

The title compound, C27H20N4O3S, crystallizes in the monoclinic system, space group P21/n, with Z = 4. The global shape of the mol-ecule is determined by the orientation of the substituents on the central 4H-1,2,4-triazole ring. The nitro-phenyl ring, phenyl ring, and naphthalene ring system are oriented at dihedral angles of 82.95 (17), 77.14 (18) and 89.46 (15)°, respectively, with respect to the triazole ring. The crystal packing features chain formation in the b-axis direction by S⋯O inter-actions. A Hirshfeld surface analysis indicates that the highest contributions to surface contacts arise from contacts in which H atoms are involved.

Design, modification of phyllanthone derivatives as anti-diabetic and cytotoxic agents.

Twelve benzylidene derivatives, one Baeyer-Villiger oxidative, six imine derivatives were successfully designed and synthesised from phyllanthone. In the search for potential new anti-diabetic agents, phyllanthone along with its benzylidene and oxidation analogues were evaluated for enzyme inhibition against α-glucosidase. In the benzylidene series, most analogues displayed stronger activity than the mother compound. Compound 1c revealed the strongest activity, outperforming the acarbose positive control with an IC50 value of 19.59 µM. Phyllanthone and its derivatives were then tested for cytotoxic activity against the K562 cell line. The imine analogues displayed the most powerful cytotoxic activity with 3cand 3d having IC50 values of 57.55 and 68.02 µM, respectively.

Synthesis and structure of (E)-N-(4-meth-oxy-phen-yl)-2-[4-(3-oxo-3-phenyl-prop-1-en-1-yl)phen-oxy]acetamide.

The title compound N-(4-meth-oxy-phen-yl)-2-[4-(3-oxo-3-phenyl-prop-1-en-1-yl)phen-oxy]acetamide, C24H21NO4, was prepared from reaction of N-(4-meth-oxy-phen-yl)-2-chloro-acetamide and (E)-3-(4-hy-droxy-phen-yl)-1-phenyl-prop-2-en-1-one, which was obtained from the reaction of 4-hy-droxy-benzaldehyde and aceto-phenone. The structure of the title compound was determined by IR, 1H-NMR, 13C-NMR and HR-MS spectroscopic data and further characterized by single-crystal X-ray diffraction. The asymmetric unit contains four mol-ecules, each displaying an E-configuration of the C=C bond. The dihedral angle between the phenyl rings in each mol-ecule varies between 14.9 (2) and 45.8 (2)°. In the crystal, C-H⋯O hydrogen-bonding inter-actions link the mol-ecules into chains running along the [001] direction. In addition, C-H⋯π inter-actions further stabilize the crystal packing. A Hirshfeld analysis indicates that the most important contributions to the surface contacts are from H⋯H (43.6%), C⋯H/H⋯C (32.1%) and O⋯H/H⋯O (18.1%) inter-actions.

Synthesis, α-glucosidase inhibition, and molecular docking studies of novel N-substituted hydrazide derivatives of atranorin as antidiabetic agents.

A series of novel N-substituted hydrazide derivatives were synthesized by reacting atranorin, a compound with a natural depside structure (1), with a range of hydrazines. The natural product and 12 new analogues (2-13) were investigated for inhibition of α-glucosidase. The N-substituted hydrazide derivatives showed more potent inhibition than the original. The experimental results were confirmed by docking analysis. This study suggests that these compounds are promising molecules for diabetes therapy. Molecular dynamics simulations were carried out with compound 2 demonstrating the best docking model using Gromac during simulation up to 20 ns to explore the stability of the complex ligand-protein. Furthermore, the activity of all synthetic compounds 2-13 against a normal cell line HEK293, used for assessing their cytotoxicity, was evaluated.

Synthesis and structure of ethyl 2-[(4-oxo-3-phenyl-3,4-di-hydro-quinazolin-2-yl)sulfan-yl]acetate.

The title compound, C18H16N2O3S, was synthesized by reaction of 2-mercapto-3-phenyl-quinazolin-4(3H)-one with ethyl chloro-acetate. The quinazoline ring forms a dihedral angle of 86.83 (5)° with the phenyl ring. The terminal methyl group is disordered by a rotation of about 60° in a 0.531 (13): 0.469 (13) ratio. In the crystal, C-H⋯O hydrogen-bonding inter-actions result in the formation of columns running in the [010] direction. Two parallel columns further inter-act by C-H⋯O hydrogen bonds. The most important contributions to the surface contacts are from H⋯H (48.4%), C⋯H/H⋯C (21.5%) and O⋯H/H⋯O (18.7%) inter-actions, as concluded from a Hirshfeld analysis.

Synthesis, structure and in vitro cytotoxicity testing of some 1,3,4-oxadiazoline derivatives from 2-hydroxy-5-iodobenzoic acid.

The syntheses of nine new 5-iodosalicylic acid-based 1,3,4-oxadiazoline derivatives starting from methyl salicylate are described. These compounds are 2-[4-acetyl-5-methyl-5-(3-nitrophenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6a), 2-[4-acetyl-5-methyl-5-(4-nitrophenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6b), 2-(4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-iodophenyl acetate, C19H17IN2O4 (6c), 2-[4-acetyl-5-(4-fluorophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate, C19H16FIN2O4 (6d), 2-[4-acetyl-5-(4-chlorophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate, C19H16ClIN2O4 (6e), 2-[4-acetyl-5-(3-bromophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6f), 2-[4-acetyl-5-(4-bromophenyl)-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6g), 2-[4-acetyl-5-methyl-5-(4-methylphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6h) and 2-[5-(4-acetamidophenyl)-4-acetyl-5-methyl-4,5-dihydro-1,3,4-oxadiazol-2-yl]-4-iodophenyl acetate (6i). The compounds were characterized by mass, 1H NMR and 13C NMR spectroscopies. Single-crystal X-ray diffraction studies were also carried out for 6c, 6d and 6e. Compounds 6c and 6d are isomorphous, with the 1,3,4-oxadiazoline ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C-H...O, C-H...π and I...π interactions. For 6e, the 1,3,4-oxadiazoline ring is almost planar. In the packing, Cl...π interactions are observed, while the I atom is not involved in short interactions. Compounds 6d, 6e, 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep-G2, with IC50 values of 0.9-4.5 µM.

Crystal structure of (E)-N'-[1-(4-amino-phen-yl)ethyl-idene]-2-hy-droxy-5-iodo-benzohydrazide methanol monosolvate.

In the title compound, C15H14IN3O2·CH3OH, two aromatic rings are linked by an N-substituted hydrazide function. The dihedral angle between the aromatic rings is 10.53 (8)°. The stereochemistry about the imine function is E. The methanol mol-ecule forms an O-H⋯O hydrogen bond to the hydrazide O atom. In the crystal, chains of mol-ecules running along the c-axis direction are formed by O-H⋯O hydrogen bonds. Adjacent chains are linked through N-H⋯O hydrogen bonds and π-π stacking inter-actions. The inter-molecular inter-actions in the crystal packing were investigated using Hirshfeld surface analysis, which indicated that the most significant contacts are H⋯H (38.2%), followed by C⋯H/H⋯C (20.6%), O⋯H/H⋯O (11.1%) and I⋯H/H⋯I (9.7%).

Crystal structure of N-(4-oxo-2-sulfanyl-idene-1,3-thia-zolidin-3-yl)-2-(thio-phen-3-yl)acetamide.

The title compound, C9H8N2O2S3, crystallizes with two mol-ecules (A and B) in the asymmetric unit. Both have similar conformations (overlay r.m.s. deviation = 0.209 Å) and are linked by an N-H⋯O hydrogen bond. In both mol-ecules, the thio-phene rings show orientational disorder, with occupancy factors of 0.6727 (17) and 0.3273 (17) for mol-ecule A, and 0.7916 (19) and 0.2084 (19) for mol-ecule B. The five-membered rings make an angle of 79.7 (2)° in mol-ecule A and an angle of 66.8 (2)° in mol-ecule B. In the crystal, chains of mol-ecules running along the a-axis direction are linked by N-H⋯O hydrogen bonds. The inter-action of adjacent chains through N-H⋯O hydrogen bonds leads to two types of ring structures containing four mol-ecules and described by the graph-set motifs R44(18) and R42(14).