Goniolanceolatins A-H, Cytotoxic Bis-styryllactones from Goniothalamus lanceolatus.

Eight new bis-styryllactones, goniolanceolatins A-H (1-8), possessing a rare α,ß-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH2Cl2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D- and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC50 values ranging from 2.3 to 4.2 µM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721, Met769, Asn818, Arg157, Ile10, and Glu12.

Synthesis, Characterization and In Vitro Antibacterial Studies of Organotin(IV) Complexes with 2-Hydroxyacetophenone-2-methylphenylthiosemicarbazone (H(2)dampt).

Five new organotin(IV) complexes of 2-hydroxyacetophenone-2-methylphenylthiosemicarbazone [H(2)dampt, (1)] with formula [RSnCl(n-1)(dampt)] (where R = Me, n = 2 (2); R = Bu, n = 2 (3); R = Ph, n = 2 (4); R = Me(2), n = 1 (5); R = Ph(2), n = 1 (6)) have been synthesized by direct reaction of H(2)dampt (1) with organotin(IV) chloride(s) in absolute methanol. The ligand (1) and its organotin(IV) complexes (2-6) were characterized by CHN analyses, molar conductivity, UV-Vis, FT-IR, (1)H, (13)C, and (119)Sn NMR spectral studies. H(2)dampt (1) is newly synthesized and has been structurally characterized by X-ray crystallography. Spectroscopic data suggested that H(2)dampt (1) is coordinated to the tin(IV) atom through the thiolate-S, azomethine-N, and phenoxide-O atoms; the coordination number of tin is five. The in vitro antibacterial activity has been evaluated against Staphylococcus aureus, Enterobacter aerogenes, Escherichia coli, and Salmonella typhi. The screening results have shown that the organotin(IV) complexes (2-6) have better antibacterial activities and have potential as drugs. Furthermore, it has been shown that diphenyltin(IV) derivative (6) exhibits significantly better activity than the other organotin(IV) derivatives (2-5).

{4-Hy-droxy-N'-[(2E,3Z)-4-oxido-4-phenyl-but-3-en-2-yl-idene]benzo-hydra-zidato}diphenyl-tin(IV) methanol monosolvate.

Two independent diphenyl-tin mol-ecules and two independent methanol mol-ecules comprise the asymmetric unit of the title compound, [Sn(C(6)H(5))(2)(C(17)H(14)N(2)O(3))]·CH(3)OH. The Sn atom in each is five-coordinated by a tridentate ligand and the ipso-C atoms of the Sn-bound benzene substituents. The resulting C(2)N(2)O donor set defines a coordination geometry that is inter-mediate between trigonal-bipyramidal (TP) and square-pyramidal (SP), with one mol-ecule slightly tending towards TP and the other slightly towards SP. The mol-ecules differ in terms of the relative orientations of the terminal benzene rings [dihedral angles = 45.71 (18) and 53.98 (17)°] and of the Sn-bound benzene substituents [dihedral angles = 59.5 (2) and 45.77 (18)°, respectively]. The most prominent feature of the crystal packing is the formation of four-mol-ecule aggregates via O-H⋯O and O-H⋯N hydrogen bonds, in which the hy-droxy group is connected to a methanol mol-ecule which, in turn, is linked to a non-coordinating N atom. Weak C-H⋯π inter-actions also occur.

{4-Hy-droxy-N'-[(2E,3Z)-4-oxido-4-phenyl-but-3-en-2-yl-idene]benzo-hydrazidato}dimethyl-tin(IV).

The Sn(IV) atom in the title compound, [Sn(CH(3))(2)(C(17)H(14)N(2)O(3))], is five-coordinated within a C(2)N(2)O donor set provided by the N,N,O-tridentate ligand and two methyl groups. The resultant coordination geometry is inter-mediate between trigonal-bipyramidal and square-pyramidal. In the crystal, supra-molecular zigzag chains propagating along the c- axis direction are mediated by O-H⋯O hydrogen bonds, and weak C-H⋯π inter-actions consolidate the packing.

1-Cyclo-hexyl-3-{(E)-[1-(pyridin-2-yl)ethyl-idene]amino}-thio-urea.

In the title thio-urea derivative, C(14)H(20)N(4)S, the non-ring non-H atoms are approximately planar, with an r.m.s. deviation of 0.0720 Å. The pyridine ring is twisted out of this plane and makes a dihedral angle of 16.85 (13)° with it. The mean plane passing through the cyclo-hexyl ring is almost normal to the central plane [dihedral angle = 69.23 (8)°]. An intra-molecular N-H⋯N(imine) hydrogen bond occurs. Centrosymmetric dimers are formed in the crystal structure via pairs of N-H⋯S hydrogen bonds, and these are connected into a supra-molecular chain along the a axis via C-H⋯π(pyrid-yl) inter-actions.

(2E)-2-[2-(Cyclo-hexyl-carbamothio-yl)hydrazinylidene]-propanoic acid.

In the title thio-urea derivative, C(10)H(17)N(3)O(2)S, the carboxyl group and the least-squares plane through the cyclo-hexyl ring are twisted out of the plane through the central CN(3)S residue; the respective dihedral angles are 7.18 (8) and 62.29 (4)°. The conformation about the azomethine bond [1.275 (2) Å] is E. The NH groups are anti, with one forming an intra-molecular N-H⋯N hydrogen bond. The main feature of the crystal structure is the formation of linear supra-molecular chains along [110] mediated by alternating pairs of O-H⋯O and pairs of N-H⋯S hydrogen bonds.

1,5-Bis[(E)-1-(2-hydroxyphenyl)ethyl-idene]thiocarbonohydrazide mono-hydrate.

In the title compound, C(17)H(18)N(4)O(2)S·H(2)O, the thio-urea derivative is almost planar, with an r.m.s. deviation for the non-H atoms of 0.057 Å. The hydroxyl groups lie to the same side of the mol-ecule as the thione S atom, a conformation that allows the formation of intra-molecular O-H⋯S and O-H⋯N hydrogen bonds. In the crystal structure, the thio-urea and water mol-ecules self-assemble into a two-dimensional array by a combination of O(water)-H⋯O(hydrox-yl), N-H⋯O(water) and O(water)-H⋯S hydrogen bonds and C-H⋯π inter-actions.

{4-Hy-droxy-N'-[(2-oxido-1-naphthyl-κO)methyl-idene]benzohydrazidato-κN',O}dimethyl-tin(IV).

Two independent but very similar mol-ecules comprise the asymmetric unit of the title compound, [Sn(CH(3))(2)(C(18)H(12)N(2)O(3))]. Each Sn atom is coordinated by two methyl groups and two O atoms and an N atom from the dinegative tridentate ligand. The resultant C(2)NO(2) donor set defines a coordination geometry inter-mediate between square-pyramidal and trigonal-pyramidal, with a small tendency towards the former. Zigzag chains running along the a axis mediated by O-H⋯N hydrogen bonding characterize the crystal packing. These are connected into layers in the ab plane by a combination of C-H⋯N and π-π [centroid-centroid distances = 3.658 (2) and 3.6740 (18) Å] inter-actions. The layers are connected along the c axis via C-H⋯O inter-actions.

n-Butyl-dichlorido(2-{(1E)-1-[2-(pyridin-2-yl)hydrazin-1-yl-idene]eth-yl}phenolato)tin(IV).

Two independent mol-ecules comprise the asymmetric unit of the title compound, [Sn(C(4)H(9))(C(13)H(12)N(3)O)Cl(2)]. The Sn atom in each is coordinated by the tridentate ligand via the phenoxide O, hydrazine N and pyridyl N atoms, forming five- and six-membered chelate rings. The approximately octa-hedral coordination geometry is completed by the α-C atom of the n-butyl group (which is trans to the hydrazine N atom) and two mutually trans Cl atoms. Differences between the mol-ecules are evident in the relative planarity of the chelate rings and in the conformations of the n-butyl groups [C-C-C-C = 177.2 (5) and -64.4 (11)°]. Significant differences in the Sn-Cl bond lengths are related to the formation of N-H⋯Cl hydrogen bonds, which link the mol-ecules comprising the asymmetric unit into dimeric aggregates. These are consolidated in the crystal packing by C-H⋯Cl contacts. The structure was refined as an inversion twin; the minor twin component is 37 (3)%.

Dichlorido{4-cyclo-hexyl-1-[1-(2-pyridyl-κN)ethyl-idene]thio-semicarbazidato-κN,S}phenyl-tin(IV).

The Sn(IV) atom in the title compound, [Sn(C(6)H(5))(C(14)H(19)N(4)S)Cl(2)], exists within a distorted octa-hedral geometry defined by the N,N',S-tridentate monodeprotonated Schiff base ligand, two mutually trans Cl atoms, and the ipso-C atom of the Sn-bound phenyl group; the latter is trans to the azo-N atom. The greatest distortion from the ideal geometry is found in the nominally trans angle formed by the S and pyridyl-N atoms at Sn [151.03 (4)°]. With the exception of the cyclo-hexyl group (chair form), the Schiff base ligand is almost planar (r.m.s. deviation of non-H and Sn atoms = 0.053 Å). The nearly orthogonal orientation of the Sn-bound phenyl group [N-Sn-C-C torsion angle = 70.8 (5)°] to the planar portion of the Schiff base allows for the formation of significant intra-molecular C-H⋯Cl inter-actions which preclude the Cl atoms from participating in N-H⋯Cl hydrogen bonds. Instead, C-H⋯π contacts, involving methyl-ene H and the Sn-bound phenyl group, lead to the formation of supra-molecular chains that pack in the bc plane. Connections between these layers are of the type C-H⋯Cl.

A Study of the in vitro cytotoxic activity of Gelsemium elegans using human ovarian and breast cancer cell lines.

The crude methanol extracts of Gelsemium elegans leaves were assessed for their cytotoxic activity using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cellular viability. This study utilized two different types of human cancer cell lines, CaOV-3 (human ovarian cancer cells) and MDA-MB-231 (human estrogen receptor negative breast cancer cells), allowing for comparison of toxicity of G. elegans against these two cancer cells lines. Our results showed that the methanol extract of G. elegans exhibited high cytotoxicity against the human ovarian cancer cell line CaOV-3 with an IC50 value of 5microg/ml after 96 h incubation. However, G. elegans displayed discernibly less toxicity against the MDA-MB-231 cells with an IC50 value 40microg/ml after 96 h incubation and this effect was dose- and time-dependent, up to 72h and 20-30 microg/ml. In conclusion, our results demonstrated that G. elegans is potently cytotoxic against the human ovarian cancer cell line CaOV-3 and to a lesser extend towards the human breast carcinoma cancer MDA-MB-231 cells, suggesting that the extract is selective towards CaOV-3 cells and may have a chemotherapeutic role for ovarian cancer treatment in the future.