Di-µ-iodido-bis-(iodido-{methyl 4-[(pyridin-2-yl-methyl-idene)amino]-benzoate-κ(2) N,N'}cadmium).

The complete binuclear molecule of the title compound, [Cd2I4(C14H12N2O2)2], is generated by the application of a centre of inversion. The Cd-I bond lengths of the central core are close and uniformly longer than the exocyclic Cd-I bond. The coordination sphere of the Cd(II) atom is completed by two N atoms of a chelating methyl 4-[(pyridin-2-yl-methyl-idene)amino]-benzoate ligand, and is based on a square pyramid with the terminal I atom in the apical position. The three-dimensional crystal packing is stabilized by C-H⋯O and C-H⋯π inter-actions, each involving the pyridine ring.

(2-{[4-(Chlorido-mercur-yl)phen-yl]imino-meth-yl}pyridine-κ(2) N,N')di-iodido-mercury(II) dimethyl sulfoxide monosolvate.

The title dimethyl sulfoxide solvate, [Hg2(C12H9ClN2)I2]·C2H6OS, features tetra-hedrally and linearly coordinated Hg(II) atoms. The distorted tetrahedral coordination sphere is defined by chelating N atoms that define an acute angle [69.6 (3)°] and two I atoms that form a wide angle [142.80 (4)°]. The linearly coordinated Hg(II) atom [177.0 (4)°] exists with a donor set defined by C and Cl atoms. Secondary inter-actions are apparent in the crystal packing with the tetra-hedrally and linearly coordinated Hg(II) atoms expanding their coordination environments by forming weak Hg⋯I [3.772 (7) Å] and Hg⋯O [2.921 (12) Å] inter-actions, respectively. Mercury-containing mol-ecules stack along the a axis, are connected by π-π inter-actions [inter-centroid distance between pyridine and benzene rings = 3.772 (7) Å] and define channels in which the dimethyl sulfoxide mol-ecules reside. The latter are connected by the aforementioned Hg⋯O inter-actions as well as C-H⋯I and C-H⋯O inter-actions, resulting in a three-dimensional architecture.

Aqua-(2-formylbenzoato)triphenyltin(IV) induces cell cycle arrest and apoptosis in hypoxic triple negative breast cancer cells.

Hypoxia plays a vital role in tumor microenvironment by allowing development and maintenance of cancer cells thereby led to major hindrance for effective anticancer therapy and main reason for failure of most anticancer drugs. We herein investigated the therapeutic efficacy and molecular mechanism of action of aqua-(2-formylbenzoato) triphenyltin (IV) compound (OTC) in MDA-MB-231 cell line. Cobalt chloride induced hypoxic MDA-MB-231 cells treated with OTC were used to access cytotoxicity, ROS, cellular apoptosis, and cell cycle progression. Further, expression of HIF-1α and VEGF, as well as apoptotic proteins like p53, Bax, Bcl-2 and caspase 3 were assessed. The findings indicated that OTC is more effective towards CoCl2 induced hypoxic cells when compared to normoxic cells and the results are far superior to doxorubicin. Additionally, our study revealed that OTC facilitates more ROS production induced cell cycle arrest and promote apoptosis. Furthermore, OTC significantly down regulates the expression of Hif-1α, VEGF and Bcl-2 in hypoxic condition and elevates the level of p53, Bax, cytochrome-C and Caspase 3. Our in vitro studies demonstrated that OTC showed better efficacy than doxorubicin, corroborating that OTC could be a promising compound for hypoxic cancer that also display multi drug resistant.

TPGS loaded triphenyltin (IV) micelles induced apoptosis by upregulating p53 in breast cancer cells and inhibit tumor progression in T-cell lymphoma bearing mice.

AIMS: Currently, breast cancer is one of the most frequently diagnosed and the second leading cause of cancer related deaths in women worldwide. Our present study aimed to investigate the major mechanistic effects of micelles (TSD-30-F, TSD-34-F) on breast cancer cells as well as their antitumor efficacy in in vivo DL bearing BALB/c mice. METHODS: Apoptotic death by micelles was investigated by mitochondrial aggregation, membrane potential and DNA fragmentation assay in MCF-7 and MDA-MB-231 cells. Molecular mode of action of micelles were determined by RT-PCR and western blot analysis, drug-ligand interaction was analyzed by in silico methods, while, in vivo antitumor activity was investigated by Kaplen-Meier survival curve, T/C value, body weight and belly size of BALB/c mice. KEY FINDINGS: TSD-30-F and TSD-34-F micelles displayed significant apoptotic induction. At molecular level, TSD-30 and TSD-34 micelles showed up-regulation of p53, Bax, Bak, Caspase-3 and down-regulation of Bcl-2 genes as well as proteins in tested breast cancer cells. In silico analysis revealed that TSD-30 and TSD-34 showed efficient binding affinity with p53, Caspase-3, Bax and Bcl-2 proteins. Significant in vivo antitumor efficacy was exhibited by the micelles formulations by increasing life span with reduced bodyweight and belly size growth pattern in BALB/c mice compared to DTX-F micelles. SIGNIFICANCE: Our results suggest that triphenyltin (IV) micelles could be a very promising therapeutic candidate for treatment of breast cancer patients and occupy a new place in targeted breast cancer therapeutic.

Dibutyltin(IV) complexes containing arylazobenzoate ligands: chemistry, in vitro cytotoxic effects on human tumor cell lines and mode of interaction with some enzymes.

Dibutyltin(IV) complexes of composition Bu2Sn(LH)2, where LH is a carboxylate residue derived from 2-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L¹H) with water molecule (1), 4-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L²H) (2) and 4-[(E)-(4-hydroxy-5-methylphenyl)diazenyl]benzoate (L³H) (3), were synthesized and characterized by spectroscopic (¹H, ¹³C and ¹¹9Sn NMR, IR, ¹¹9Sn Mössbauer) techniques. A full characterization was accomplished from the crystal structure of complex 1. The molecular structures and geometries of the complexes (1a i.e. 1 without water molecule and 3) were fully optimized using the quantum mechanical method (PM6). Complexes 1 and 3 were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. Compound 3 is found to be four times superior for the A498, EVSA-T and MCF-7 cell lines than CCDP (cisplatin), and four, eight and sixteen times superior for the A498, H226 and MCF-7 cell lines, respectively, compared to ETO (etoposide). The mechanistic role of cytotoxic activity of test compounds is discussed in relation to the theoretical results of docking studies with some key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II associated with the propagation of cancer.

Bis{2-[(E)-(5-tert-butyl-2-hy-droxy-phen-yl)diazen-yl]benzoato}dimethyl-tin(IV).

In the title diorganotin dicarboxyl-ate, [Sn(CH(3))(2)(C(17)H(17)N(2)O(3))(2)], the tin(IV) atom is six-coordinated by four O atoms derived from asymmetrically coordinating carboxyl-ate ligands, and two methyl-C atoms. The resulting C(2)O(4) donor set defines a skew-trapezoidal bipyramid with the Sn-C bonds disposed over the weaker Sn-O bonds. Within each carboxyl-ate ligand, the hydroxyl-H atom forms bifurcated O-H⋯(O,N) hydrogen bonds with carboxyl-ate-O and azo-N atoms. The dihedral angles between the benzene rings in the two ligands are 10.44 (11) and 34.24 (11)°. In the crystal, centrosymmetric dimers are formed through pairs of Sn⋯O inter-actions [2.8802 (16) Å], and the dimers are linked into supra-molecular layers in the ac plane by C-H⋯π inter-actions.

Structural diversity among some dialkyltin(IV) benzoate and related derivatives.

The molecular structures of five diorganotin(IV) carboxylates, (I)-(V), can be categorized into two main well-known structural types for such Sn complexes. One is the mononuclear dialkytin(IV) carboxylates with an [R2Sn(LH)2]-type skew-trapezoidal bipyramid, where the alkyl ligands are in pseudo-axial positions and the O atoms from two asymmetrically coordinated bidentate carboxylate ligands are in the equatorial plane. This structure type is adopted by dibutylbis{(E)-2-hydroxy-5-[(3-methylphenyl)diazenyl]benzoato}tin(IV) cyclohexane hemisolvate, [Sn(C4H9)2(C14H11N2O3)2]·0.5C6H12, (I), dibenzylbis{(E)-5-[(4-bromophenyl)diazenyl]-2-hydroxybenzoato}tin(IV), [Sn(C7H7)2(C13H8BrN2O3)2], (II), and aquadibenzylbis(4-{(E)-[(Z)-4-hydroxypent-3-en-2-ylidene]amino}benzoato)tin(IV) benzene disolvate, [Sn(C7H7)2(C12H12NO3)2(H2O)]·2C6H6, (III), although the latter has an additional water ligand to give a distorted pentagonal bipyramidal coordination geometry in which the carboxylate groups are more symmetrically coordinated to the Sn atom than in (I) and (II). The other structure motif is that of the tetranuclear bis(dicarboxylatotetraorganodistannoxanes), {[R2Sn(LH)]2O}2, which contain an Sn4O2 core decorated with four bridging carboxylate ligands, plus two alkyl ligands at each SnIV centre. The complexes octabutyltetrakis{µ-(E)-4-[(4-hydroxy-3,5-dimethylphenyl)diazenyl]benzoato}di-µ3-oxido-tetratin(IV) ethanol disolvate, [Sn4(C4H9)8(C15H13N2O3)4O2]·2C2H6O, (IV), and octabutyltetrakis{(E)-3-[(2-hydroxybenzylidene)amino]propanoato}di-µ3-oxido-tetratin(IV), [Sn4(C4H9)8(C10H10NO3)4O2], (V), display this motif. The structures obtained correlate with the 1:1 and 1:2 stoichiometric ratios of the dialkyltin(IV) and carboxylic acid starting materials in the syntheses. The supramolecular structures arising from consideration of secondary Sn...O interactions and/or classic hydrogen bonds include discrete molecules for (V), centrosymmetric dimers for (I), extended chains for (II) and (III), and sheets for (IV).

In vitro cytotoxic evaluation of novel dichlorodiorgano[N-(2-pyridylmethylene)arylamine]tin(IV) derivatives in human tumor cell lines.

The present report overviews the studies on diorganotin(IV) complexes of N-(2-pyridylmethylene)arylamine, R(2)SnCl(2).L (R = Me (1), Et (2), Bu (3) or Ph (4)) as cytotoxic agents. This family of complexes was designed to include highly electron-donating N;Nchelating ligand to afford octahedral R(2)SnCl(2).L complexes of relatively high hydrolytic stability, with the aim to retain ligand binding throughout the biological activity for achieving controlled processes and allowing mechanistic evaluation. It is observed that the high cytotoxic activity is dependent on the Sn-R groups and Sn-N bond lengths, and which is related to the cytotoxic potential. Complex (2) was found to exhibit stronger cytotoxic activity in vitro particularly for A498 (renal cancer), IGROV (ovarian cancer), MCF-7 (breast cancer), and WIDR (colon cancer) of human tumour cell lines and the results are far superior to standard reference drugs e.g., doxorubicin, cisplatin, 5-fluorouracil, methotrexate, etoposide including paclitaxel. The important insights gained with the diorganotin(IV) compounds in regards to their cytotoxic activity are discussed.

Triphenyltin(IV) 2-[(E)-2-(aryl)-1-diazenyl]benzoates as anticancer drugs: synthesis, structural characterization, in vitro cytotoxicity and study of its influence towards the mechanistic role of some key enzymes.

Triphenyltin(IV) complexes of composition [Ph(3)SnL(1)H](n) (1) and [Ph(3)SnL(2)H](n) (2) (where L(1)H = 2-[(E)-2-(3-formyl-4-hydroxyphenyl)-1-diazenyl]benzoate and L(2)H = 2-[(E)-2-(4-Hydroxy-5-methylphenyl)-1-diazenyl]benzoate) were synthesized and characterized by spectroscopic ((1)H, (13)C and (119)Sn NMR, IR, (119)Sn Mössbauer) techniques in combination with elemental analysis. The molecular structures and geometries of the complexes (1 and 2) were fully optimized using the quantum mechanical method (PM3). Complexes (1 and 2) were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumour cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The test compounds 1 and 2 exhibit comparable results and both the compounds are found to be far superior to CCDP (cisplatin), 5-FU (5-fluorouracil) and ETO (etoposide) across a panel of cell lines and the activity is more pronounced for the A498 (22 fold) and H226 (33 fold) cell lines compared to CCDP, and A498 (13 fold), H226 (39 fold) and MCF-7 (33 fold) cell lines compared to ETO. The test compounds are even 23 fold more active in magnitude in terms of the ID(50) value at least against the H226 cell lines when compared with MTX (methotrexate). Further, the mechanistic role of cytotoxic activity of test compounds (1 and 2), are discussed in relations to the theoretical results of docking studies with some of the key enzymes such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II.

Tetrakis(mu2-4-aminobenzoato)di-mu3-oxido-tetrakis[dibutyltin(IV)].

The molecule of the title compound, [Sn(4)(C(4)H(9))(8)(C(7)H(6)NO(2))(4)O(2)], lies about an inversion centre and is a tetranuclear bis(tetrabutyldicarboxylatodistannoxane) complex containing a planar Sn(4)O(2) core in which two mu(3)-oxide O atoms connect an Sn(2)O(2) ring to two exocyclic Sn atoms. Each Sn atom has a highly distorted octahedral coordination. In the molecule, the carboxylate groups of two aminobenzoate ligands bridge the central and exocyclic Sn atoms, while two further aminobenzoate ligands have highly asymmetric bidentate chelation to the exocyclic Sn atoms plus long O...Sn interactions with the central Sn atoms. Each Sn atom is also coordinated by two pendant n-butyl ligands, which extend roughly perpendicular to the plane of the Sn(4)O(10) core. Only one of the four unique hydrogen-bond donor sites is involved in a classic N-H...O hydrogen bond, and the resulting supramolecular hydrogen-bonded structure is an extended two-dimensional network which lies parallel to the (100) plane and consists of a checkerboard pattern of four-connected molecular cores acting as nodes. The amine groups not involved in the hydrogen-bonding interactions have significant N-H...pi interactions with neighbouring aminobenzene rings.

4-[(E)-(5-tert-Butyl-2-hydroxy-phen-yl)diazen-yl]benzoic acid benzene hemisolvate.

The title benzene hemisolvate, C(17)H(18)N(2)O(3)·0.5C(6)H(6), features an essentially planar (the r.m.s. deviation of the non-H atoms, excluding methyl-C, is 0.071 Å) diazo mol-ecule with an E conformation about the N=N bond, and a half-mol-ecule of benzene disposed about a centre of inversion. The dihedral angle formed between the benzene rings of the diazo mol-ecule is 7.69 (12)°. In the crystal, centrosymmetrically related dimers associate via the eight-membered carboxylic acid dimer synthon, {⋯HOC(=O)}(2), and these are connected into a supra-molecular chain along the b axis via C-H⋯O contacts.

p53-dependent antiproliferative and antitumor effect of novel alkyl series of diorganotin(IV) compounds.

PURPOSE: A series of diorganotin(IV) dichloride complexes of N-(2-pyridylmethylene)arylamine (nitrogen-chelating ligands) have been synthesized and characterized. The present study was carried out to investigate the comparative anti-proliferative and anti-tumor effect of Me(2)SnCl(2.)L(1) (OTC-1), Et(2)SnCl(2.)L(2) (OTC-2) and (n)Bu(2)SnCl. L(2) (OTC-3) in combination with X-rays (1.5 Gy). METHOD: The cytotoxicity of these diorganotin(IV) compounds was studied in human peripheral lymphocytes and the antitumor activity was assessed in Dalton's lymphoma cells. The involvement of proteins that regulate cell cycle and apoptosis was investigated to elucidate the mechanism of their action. RESULTS: 5 mg kg(-1) of OTC-3 showed better antiproliferative and antitumor activity than OTC-1 and OTC-2, both as alone or in combination with X-rays. The maximum enhancement of exchange aberrations and the level of p53 and p16 proteins were observed in the OTC-3 treated samples. Upregulated expression of p53 caused a significant down-regulated transcriptionally repression of Survivin in OTC-3 treated human lymphocytes. CONCLUSION: It could be possible that after treatment with either OTC-3 alone or in combination with X-rays the Dalton's lymphoma cells may die apoptotically after inducing initial delay in cell cycle and thereby survivality of mouse bearing Dalton's Lymphoma cells was increased significantly.

An ortho-rhom-bic polymorph of 5-[(4-methyl-phen-yl)diazen-yl]salicylaldehyde.

The title compound, C(14)H(12)N(2)O(2), is an ortho-rhom-bic polymorph of the previously reported monoclinic form [Bakir et al. (2005 ▶). Acta Cryst. E61, o1611-o1613]. The dihedral angle between the aromatic rings is 4.32 (13)°. The mol-ecular structures of the two polymorphs, including short intra-molecular O-H⋯O hydrogen bonds between the the hydr-oxy and keto groups, are quite similar but their crystal packings are distinct. Unlike the monoclinic form, in which centrosymmetrically related hydr-oxy and keto groups form {⋯H⋯O}(2) synthons via weak O-H⋯O contacts, leading to dimeric aggregates, in the ortho-rhom-bic form, the hydrogen bonding between these groups leads to the formation of supra-molecular chains orientated along the a axis.

2-[(E)-(5-tert-Butyl-2-hydroxy-phen-yl)-diazen-yl]benzoic acid.

The title compound, C(17)H(18)N(2)O(3), is approximately planar, owing in part to an intra-molecular bifurcated O-H⋯(N,O) hydrogen bond; the dihedral angle between the two aromatic rings is 23.86 (9)°. In the crystal struture, centrosymmetrically related mol-ecules associate into dimers via the eight-membered carboxyl-ate {⋯H-O-C=O}(2) synthon.

Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity.

Eight Ti(iv) compounds 1-8, of the type [Ti(Ln)2] where Ln is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2'-hydroxyacetophenone and titanium(iv) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of 1-6 and 7·CH2Cl2 were deduced from the single crystal X-ray diffraction data, which indicated that each L2- ligand is fully deprotonated and coordinated to the Ti(iv) cation via the enolic oxygen, the imino nitrogen and the phenolic oxygen atoms (ONO donor set) in an enol tautomeric form, the metal assuming the distorted octahedral geometry. The structures of pro-ligands H2L3 and H2L5 are also reported. All complexes displayed high hydrolytic stability. In vitro cytotoxicity assays towards human ovarian A2780 and colon HT-29 cancer cell lines revealed the activity dependence on the acylhydrazone substituents, with electron-donating groups on the phenolato units enhancing the solubility and promoting cytotoxicity. The lead compound 5 of this study presents IC50 values of 2.5 ± 0.2 and 4.2 ± 0.6 µM for ovarian A2780 and colon HT-29 human cancer cells, respectively.

Triphenylstannyl((arylimino)methyl)benzoates with selective potency that induce G1 and G2/M cell cycle arrest and trigger apoptosis via ROS in human cervical cancer cells.

Metal complexes with organelle specificity and potent but selective cytotoxicity are highly desirable. A novel series of triphenylstannyl 4-((arylimino)methyl)benzoates (2-8) were obtained by the reactions of triphenylstannyl 4-formylbenzoate [Ph3Sn(L1)] 1 with primary aromatic amines. Two representative compounds (10, 11) were also synthesized by reacting aqua-triphenylstannyl 2-formylbenzoate [Ph3Sn(L9)(H2O)] (9) with aniline and p-fluoroaniline, respectively. These compounds were characterized by elemental analysis, IR and 1H, 13C and 119Sn NMR spectroscopy, as well as single-crystal X-ray diffraction for compounds 5, 7-11 and three pro-ligands. The in vitro cytotoxic activities of 1-11 were assessed using the MTT tetrazolium dye assay against HeLa (human cervical) and MDA-MB-231 (breast) cancer cells, with IC50 values revealing high activity. Compared to cisplatin, compounds 1-11 exhibited enhanced cytotoxic efficacy, indicating their potential as potent anticancer agents. Among these, 1 and 5 demonstrated maximum inhibition in HeLa cells, with negligible effect on normal human embryonic kidney (HEK) cells. The combined results of the DCFH-DA dye and Hoechst 33342/PI nuclear staining assays, along with flow cytometry analysis, show that they possess a dual mode of action: They induced apoptotic cell death, attributable to the tin-assisted generation of reactive oxygen species. Cell cycle analyses indicated that compounds 1 and 5 exhibit cell growth inhibition and may cause turbulences in the G1 and G2/M phases.

Electrospray ionization-multistage tandem mass spectrometry of complex multitin organometallic compounds.

The series of 14 complex organotin(IV) compounds containing many tin atoms and noncovalent bonds in the structure was characterized by electrospray ionization multistage tandem mass spectrometry (ESI-MS(n)). The mass spectra were measured in both polarity modes to obtain complementary structural information. The characteristic pattern of ten natural tin isotopes allowed the determination of the number of tin atoms in the molecular adducts and fragment ions by comparing theoretical and experimental isotopic distributions. Positive ion ESI spectra show unusual adduct formation depending on the type of organic solvent used for the direct infusion analysis owing to the ion-molecule reactions in the ion source. On the basis of the detailed spectral interpretation of organotin(IV) compounds, the fragmentation patterns of multitin organometallic compounds have been proposed. Noncovalent bonds in polymeric complexes are fragmented first, which is then followed by characteristic neutral losses in monomeric units.

Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable apoptosis mediated by reactive oxygen species.

The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3; isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6 are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR (1H, 13C, 119Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50 value of 1.19 and 1.44µM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50 value of 0.88µM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.

New dibutyltin(IV) ladders: Syntheses, structures and, optimization and evaluation of cytotoxic potential employing A375 (melanoma) and HCT116 (colon carcinoma) cell lines in vitro.

Synthesis and spectroscopic properties of seven new dibutyltin(IV) compounds of 2-{(E)-4-hydroxy-3-[(E)-4-(aryl)iminomethyl]phenyldiazenyl}benzoic acids (LnHH'; n=2-8) with general formula {[Bu2Sn(LnH)]2O}2 (1-7) are reported. The compounds were characterized by elemental analysis and by UV-Visible, fluorescence, IR, 1H, 13C and 119Sn NMR spectroscopies. Solid state structures of dibutyltin(IV) compounds 1-3, 6 and 7 were accomplished from single crystal X-ray crystallography which reveal the common ladder-type structure with two endo- and two exo-Sn atoms. The redox properties of LnHH' (n=2-4, 7 and 8) and their diorganotin(IV) compounds 1-3, 6 and 7 were also investigated by cyclic voltammetry. In general, the dibutyltin(IV) derivatives exhibited significant in vitro cytotoxic potency towards A375 (melanoma) and HCT116 (colon carcinoma) cell lines as determined by several experiments, like Live and Dead assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), cleavage of caspases and PARP (poly(ADP-ribose)polymerase), and DNA fragmentation. Dibutyltin(IV) compounds increase cell death without cytolysis and decreases membrane fluidity, without interfering with p53. Among the dibutyltin(IV) compounds, compound 6 was found to be the most potent, with an IC50 value of 78nM. A mechanism of action for tumor cell death is proposed.

Synthesis, photophysical properties and structures of organotin-Schiff bases utilizing aromatic amino acid from the chiral pool and evaluation of the biological perspective of a triphenyltin compound.

Five new organotin(IV) complexes of compositions [Me2SnL1] (1), [Me2SnL2]n (2), [Me2SnL3] (3), [Ph3SnL1H]n (4) and [Ph3SnL3H] (5) (where L1=(2S)-2-((E)-((Z)-4-hydroxypent-3-en-2-ylidene)amino)-3-(1H-indol-3-yl)propanoate, L2=(2S)-(E)-2-((2-hydroxybenzylidene)amino)-3-(1H-indol-3-yl)propanoate and L3=(2S)-(E)-2-((1-(2-hydroxyphenyl)ethylidene)amino)-3-(1H-indol-3-yl)propanoate were synthesized and spectroscopically characterized. The crystal structures of 1-4 were determined. For the dimethyltin derivative 2, a polymeric chain structure was observed as a result of a long Sn∙∙∙O contact involving the exocyclic carbonyl oxygen-atom from the tridentate ligand of a neighboring Sn-complex unit. The tin atom in this complex has a distorted octahedral coordination geometry, in which the long Sn-O bond is almost trans to the tridentate ligand nitrogen-atom. In contrast, the dimethyltin(IV) complexes 1 and 3 displayed discrete monomeric structures where the tin atom has distorted trigonal-bipyramidal geometry with the two coordinating L oxygen atoms defining the axial positions. On the other hand, 4 is a chain polymer in the solid state. The ligand-bridged Sn atoms adopt a trans-Ph3SnO2 trigonal-bipyramidal configuration with equatorial phenyl groups. A carboxylato oxygen atom from one and the hydroxyl oxygen of the successive ligand in the chain occupy the axial positions. The solution structures were predicted by the use of 119Sn NMR chemical shifts. The photophysical properties of the complexes were investigated in the solid and in solution. The triphenyltin(IV) compound 4 was tested in detail ex vivo against A375 (human melanoma) cell line, exhibiting an IC50 value of 261nM to induce cell death as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay without significant alteration of cytolysis as determined by lactate dehydrogenase (LDH) assay. Compound 4-mediated potent cell death was also determined by Live and Dead assay and caspase-mediated cleavage of poly-ADP ribose polymerase (PARP). Potent cell death activity was not observed in primary cells, like blood-derived peripheral mononuclear cells (PBMC). Compound 4 inhibited the diphenyl hexatriene (DPH) binding to cells and decreased the micro viscosity in a dose-dependent manner. Additionally, the ability of 4 and cyclodextrin (CD) to interact was determined by molecular modelling.