Synthesis, structural determination and photo-antiproliferative activity of new 3-pyrazolyl or -isoxazolyl substituted 4-hydroxy-2(1H)-quinolinones

A convenient route to new 3-quinolinonyl-pyrazoles and isoxazoles is described through cyclization of 3-[(E)-3-(dimethylamino)-2-propenoyl]-4-hydroxy-1-methyl-2(1H)-quinolinone. The phototoxicity as well as the cytotoxic activities of the title compounds are evaluated against leukemia- and adenocarcinoma-derived cell lines in comparison to the normal human keratinocytes.     

纳米尺寸多酸脂质体复合物的合成及抗肿瘤活性研究

合成了杂多化合物α-K₈H₆[Si₂W₁₈Ti₆O₇₇](α-Si₂W₁₈Ti₆)的脂质体纳米粒子.通过红外、固体核磁和极谱对其结构进行了表征,使用透射电镜和粒径分析仪研究了纳米粒子的形态和粒径分布.所合成的纳米粒子中多酸化合物仍保持母体的结构,纳米粒子的粒径在60～150nm之间.用MTT法测定了不同粒径纳米粒子的体外抗肿瘤活性.发现多酸化合物形成脂质体纳米粒子后稳定性和活性都有所提高.     

Synthesis and characterization of dinuclear pyrazolato bridged platinum(IV) complexes

Reactions of [PtMe₃(OCMe₂)₃](BF₄) and [(PtMe₃I)₄] with pyrazole (pzH) afforded mononuclear pyrazole platinum(IV) complexes [PtMe₃(pzH)₃](BF₄) (1) and [PtMe₃I(pzH)₂] (2), respectively. The formation of dinuclear pyrazolato bridged platinum(IV) complexes (PPN)[(PtMe₃)₂(μ-pz)₃] (3), (PPN)[(PtMe₃)₂(μ-I)(μ-pz)₂] · 1/2Et₂O (4) and [K(18C6)][(PtMe₃)₂(μ-I)(μ-pz)₂] (5) was achieved by the reaction of each 1 and 2 with [PtMe₃(OCMe₂)₃](BF₄) in the presence of KOAc followed by reaction with (PPN)Cl (PPN⁺ = bis(triphenylphosphine)iminium cation) and 18C6, respectively. The reaction of complex 4 with AgO₂CCF₃ followed by addition of RSR′ (R/R′ = Me/Me, Me/Ph) resulted in the formation of complexes [(PtMe₃)₂(μ-pz)₂(μ-RSR′)] (R/R′ = Me/Me, 6; Me/Ph, 7). All complexes were characterized unambiguously by microanalysis and NMR (¹H, ¹³C) spectroscopic investigations. Additionally, crystal structures of complexes 3 and 4 as well as DFT calculation are presented. Furthermore, in vitro studies on the anti-proliferative activity of complexes 2 and 5 were carried out.     

Synthesis and biological activity of triorganogermanium substituted heteropolytungstates

Four new compounds, [Me₄N]₄H₅[(RGe)₃(XW₉O_34−n)₂] (R = HOOCCH₂CH₂, HOOCCH₂(m-NO₂C₆H₄)CH, X = P, n = 0; X = Sb, n = 1) have been prepared from trichlorogermanium precursors and lacunary polyoxometallates ([PW₉O₃₄]⁹⁻ and [SbW₉O₃₃]⁹⁻). The products were characterized by means of elemental analysis, IR spectroscopy, ¹H NMR and ¹⁸³W NMR spectroscopy. ¹⁸³W NMR spectra of the complexes support the stoichiometry of the new heteropolyanions and the probable retention of the XW₉ units in water. The organogermanium substituted complexes showed promising activity against two human tumor cell lines (leucocythemia Hela cells and S180 cells) in vitro and [Me₄N]₄H₅[(HOOCCH₂CH₂Ge)₃(SbW₉O₃₃)₂] exhibited some certain antitumoral activity in vivo and can increase the immune ability of the spleen.     

The marine sponge Plakortis zyggompha: a source of original bioactive polyketides

Three new spiculoic acids 1-3 and two members of a new closely related family of natural products named zyggomphic acids 4 and 5 were isolated from the very little studied marine sponge Plakortis zyggompha. Both families of compounds share a unique trans-hydrindan-2-one skeleton with six stereogenic centers. A total of 15 new metabolites were isolated from this sponge, all are of polyketide origin. The structures were elucidated using LC-MS, 1D, and 2D NMR methods. The absolute stereochemistry was determined by circular dichroism. The large number of close bioactive analogues allowed us to propose preliminary structure-activity relationships as antitumoral and antimycobaterial agents.     

Synthesis,characterization, X-ray structure and preliminary in vitro antitumor activity of the nitrosyl complex fac-[RuCl3(NO)(dppf)], dppf = 1,1′-bis(diphenylphosphine)ferrocene

The reaction of RuCl₃NO · 2H₂O with stoichiometric amount of dppf, 1,1′-bis(diphenylphosphino)ferrocene, afforded the new neutral nitrosyl complex fac-[RuCl₃(NO)(dppf)] which was characterized by spectroscopical, electrochemical and X-ray crystallography techniques as well as elemental analysis. The ν_NO band in the IR spectrum is at 1860 cm⁻¹ (CH₂Cl₂ solution) and in the cyclic voltammogram an irreversible wave was observed at −1.35 V, both are characteristics of a nitrosonium (NO⁺) character for the coordinated NO. Additionally, preliminary in vitro antitumor activity against the MDA-MB-231 breast tumor cell line was carried out for the new complex. The initial results indicated an important activity for fac-[RuCl₃(NO)(dppf)] (IC₅₀ = 10 ± 3 μM ). The complex has a higher cytotoxicity than the precursor complex RuCl₃NO · 2H₂O, the free dppf ligand as well as the reference metallodrug cisplatin.     

QSAR of copper(II) complexes with cytotoxic properties

Summary A QSAR based on a multiple regression analysis for 15 copper(II) semi- and thiosemicarbazone complexes with cytotoxic properties is presented. In vitro cytotoxicity was selected as the dependent variable and Van der Waals volumes (Vm), octanol- water partition coefficients (logP), specific rate constants of the copper(II) complexes towards superoxide radicals (k _s ) and variation in C=N vibration bands (CN) in IR spectra of the complexes with respect to the free ligands were selected as the independent variables. The stepwise regression procedure and the all possible regressions were practiced in the analysis of the data. The orthogonality analysis proved noncollinearity among the variables. According to the obtained equation the two best copper(II) complexes were submitted to a broad in vivo screening study and resulted to be active against La, P-388 and L-1210 leukemias.

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QSAR von Kupfer(II)-Komplexen mit cytotoxischen Eigenschaften

Zusammenfassung Es wird eine quantitative Struktur-Aktivitäts-Beziehung basierend auf einer multiplen Regressionsanalyse für 18 Kupfer(II)-Semi- und Thiosemicarbazon-Komplexe präsentiert. Die in vitro-Cytotoxizität wurde als die abhängige Variable und Van-der-Waals-Volumina (Vm), Octanol-Wasser-Verteilungskoeffizienten (logP), spezifische Geschwindigkeitskonstanten der Kupfer(II)-Komplexe gegenüber Superoxid-Radikalen (k _s ) und die Variationen der C=N-Vibrationsbanden (CN) in den IR-Spektren der Komplexe gegenüber den freien Liganden als unabhängige Variablen eingeführt. Es wurde stufenweise Regression und die alle möglichen Regressionen-Prozedur in der Analyse der Daten verwendet. Die Orthogonalitätsanalyse zeigte Nichtkolinearität der Variablen an. Entsprechend den erhaltenen Gleichungen wurden die beiden besten Kupfer(II)-Komplexe einem breiten in vivo-Screening unterworfen. Sie waren gegenüber La, P-388 und L-1210 Leukemie aktiv.

     

Reactivite du Bis(dichlorophosphoryl)imide Vis a Vis de La N,N-Bis(2-chloroéthyl)-amine Application a la Synthese de Molecules Susceptibles de Presenter une Activite Antitumorale

The reaction of bis(dichlorophosphoryl)imide HN(P(O)Cl 2 ) 2 1 , with N,N-bis(2-chloroethyl)amine HN(CH 2 CH 2 Cl) 2 (bCEA), has been studied in order to synthesize Phosphorus-Nitrogen derivatives which present anti-tumoral activity. It has been possible to show the formation of the mono 2 , di 3 and tetrasubstituted 4 derivatives as well as the existence of diastereoisomers for 2 and 3 . The combined use of NMR ( 31 P, 13 C) and mass spectrometry has allowed us to show the instability of the tetrasubstituted derivative wich is transformed to the O-alkylated compound 4a with elimination of HCl. We studied also the cosubstitution reactions of 1 by HN(CH 2 CH 2 Cl) 2 and ammonia on the one hand, HN(CH 2 CH 2 Cl) 2 and glycine ethyl ester on the other hand. Spectroscopic studies of the resulting products revealed the involvement of N-alkylation reactions leading to 6 and 7 . The study of the antitumoral activity of these compounds was undertaken. Only the phosphazene derivative 2 which contains a bifunctionnal alkylating agent exhibited a moderate anti-tumoral activity.     

杂多酸环戊二烯钒衍生物的合成、谱学性质及抗肿瘤活性

合成了杂多酸环戊二烯钒衍生物[Bu₄N]₄[(CpV)PW₁₁O₃₉](1),[Bu₄N]₄H[(CpV)SiW₁₁O₃₉](2)和[Bu₄N]₄[A-β-(η5-CpV)SiW₉V₃O₄₀](3),并通过元素分析、IR、51V和183W NMR谱进行了结构表征。结果表明配合物(1)和(2)为结合型有机金属配合物,(3)为支撑型杂多酸有机金属配合物。体外抗肿瘤活性研究表明化合物(1)对HL-60和B₁₆均具有一定的抑制作用。     

Short synthesis of noscapine, bicuculline, egenine, capnoidine, and corytensine alkaloids through the addition of 1-siloxy-isobenzofurans to imines

A concise diastereotioselective strategy for the synthesis of noscapine, bicuculline, and egenine (1a-c), as well as capnoidine and corytensine (2a,b), was developed using diastereoselective addition of 1-siloxy-isobenzofurans 4a and 4b to iminium ion 5 in a one-pot approach. The synthesis features the use of imine 13 obtained through Bischler-Napieralsky reaction from amine 11. The addition of ionic liquids as addictives in the reactions afforded erythro configuration in major adduct compounds. The synthetic route can also be applied in the total synthesis of promising tubulin binding agent EM105 (3).