N-{2-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]ethyl}-3-methoxybenzamide: design, synthesis, crystal structure, antiproliferative activity, DFT, Hirshfeld surface analysis and molecular docking study.

The compound N-{2-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]ethyl}-3-methoxybenzamide (8) was synthesized by the condensation of 3-methoxybenzoic acid (7) with N1-(2-chlorothieno[3,2-d]pyrimidin-4-yl)ethane-1,2-diamine (6). This intermediate was prepared from methyl 3-aminothiophene-2-carboxylate (1) by the condensation with urea, chlorination with phosphorus oxychloride and then condensation with ethane-1,2-diamine. The crystal structure of the title compound was determined and the crystal of the title compound belongs to the tetragonal system, space group P4(3) with a = 9.4694(10) Å, b = 9.4694(10) Å, c = 18.886(3) Å, α = 90°, ß = 90°, γ = 90°. The optimized geometric bond lengths and bond angles obtained by using density functional theory (DFT) have been compared with X-ray diffraction values. The calculated HOMO and LUMO energies showed the character of the title compound. The molecular electrostatic potential (MEP) surface map of the related molecule was investigated with theoretical calculations at the B3LYP/6-311 + G(d,p) levels. A quantitative analysis of the intermolecular interactions in the crystal structures has been performed using Hirshfeld surface analysis. In addition, the title compound possesses marked inhibition against the proliferation of human colon cancer cell line HT-29 (IC50 = 1.76 µM), human lung adenocarcinoma cell line A549 (IC50 = 1.98 µM) and human gastric cancer cell line MKN45 (IC50 = 2.32 µM), displaying promising anticancer activitiy. The molecular docking studies revealed that the title compound may exhibit activity inhibiting PDB:3D15.Communicated by Ramaswamy H. Sarma.

Spherical trihedral metallo-borospherenes.

The discovery of borospherenes unveiled the capacity of boron to form fullerene-like cage structures. While fullerenes are known to entrap metal atoms to form endohedral metallofullerenes, few metal atoms have been observed to be part of the fullerene cages. Here we report the observation of a class of remarkable metallo-borospherenes, where metal atoms are integral parts of the cage surface. We have produced La3B18- and Tb3B18- and probed their structures and bonding using photoelectron spectroscopy and theoretical calculations. Global minimum searches revealed that the most stable structures of Ln3B18- are hollow cages with D3h symmetry. The B18-framework in the Ln3B18- cages can be viewed as consisting of two triangular B6 motifs connected by three B2 units, forming three shared B10 rings which are coordinated to the three Ln atoms on the cage surface. These metallo-borospherenes represent a new class of unusual geometry that has not been observed in chemistry heretofore.

Molecule action mechanisms of NM-3 on human gastric cancer SGC-7901 cells in vivo or in vitro.

AIM: To study the molecule action mechanisms of NM-3 on the growth of human gastric cancer SGC-7901 cells in vivo or in vitro. METHODS: SGC-7901 from human non-differentiated gastric cancer cell line was cultured with NM-3 at 100 mg/ml for 24 h. We observed its inhibitory rate and the density of micro-vascular growth in grafted mice with human gastric cancer SGC-7901. The apoptosis of human gastric cancer SGC-7901 was revealed in NM-3 treatment group by using terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate-fluorescene nick end labeling (TUNEL) method and flow cytometry analysis. RESULTS: The growth of SGC-7901 cells was markedly inhibited compared with control growp, which was smaller than that in normal saline control group (4.17 g+/-0.22 g vs 9.45 g+/-1.38 g, P<0.01). The level of apoptosis of human gastric cell line SGC-7901 was obviously increased in NM-3 treatment group at 1 mg.L(-1) for 24 h. NM-3 inducing apoptotic index in NM-3 plus carboplatin group was 3.5 times that of carboplatin control group (TUNEL: 27.98+/-6.12% vs 12.94+/-2.12%, FACScan: 26.86+/-5.69% vs 11.86+/-1.09%, P<0.01). Western blot analysis showed that the apoptotic index of human gastric cancer was elevated for 12, 24 and 36 h with an evident time-effect relationship in groups at 100 mg.L(-1). NM-3 enhanced the inhibitive effects and sensitivity of chemotherapy for human gastric cancer in nude mice. These results suggested that NM-3 played a key inhibitive role in the growth of grafted human gastric cancer in nude mice. CONCLUSION: NM-3 can inhibit the growth of human gastric cancer cell line SGC-7901, and enhance the sensitivity of carboplatin on SGC-7901 and induced its apoptosis.