K[Pt(NH3)Cl3], a valuable precursor for the preparation of platinum complexes with cytostatic activity, e.g. satraplatin, picoplatin, LA-12 and cycloplatam, is currently prepared from cis-[Pt(NH3)2Cl2] or K2[PtCl4] and these are the usual impurities in the final product. A simple, selective and sensitive HPLC-UV analytical method for the determination of the purity of K[Pt(NH3)Cl3] and the quantification of the impurities has been developed and validated. The platinum complexes present in the final product were separated on a strong base ion exchange column by the gradient elution with detection at 213 nm. Intra-assay precisions for the platinum complexes respective to their ions ([PtCl4]2?, [Pt(NH3)Cl3]? and cis-[Pt(NH3)2Cl2]) were between 0.1 and 2.0% (relative standard deviation); intermediate precisions were between 1.4 and 2.0% and accuracies were between 98.6 and 101.4%. Limits of detection of [PtCl4]2?, [Pt(NH3)Cl3]? and cis-[Pt(NH3)2Cl2] were 6 µg · ml?1, 13 mg · ml?1 and 5 µg · ml?1 respectively, limits of quantification of [PtCl4]2?, [Pt(NH3)Cl3]? and cis-[Pt(NH3)2Cl2] were 51 µg · ml?1, 55 mg · ml?1 and 20 µg · ml?1 respectively. 相似文献
A series of novel N‐(substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones 5a – 5o were synthesized with substituted benzylamines as raw materials via a series of Michael addition, Dieckmann condensation, hydrolysis decarboxylation and aldol condensation. The structures were confirmed by 1H NMR, IR, MS techniques and elemental analysis. Assay‐based antiproliferative activity study using leukemic cell lines K562 revealed that most of the title compounds have high effectiveness in inhibiting leukemia K562 cells proliferation, among which the compounds 5g (IC50=7.81 µg·mL−1), 5k (IC50=6.35 µg·mL−1), 5l (IC50=7.20 µg·mL−1), and 5o (IC50=5.79 µg·mL−1) have better inhibition activities than standard 5‐fluorouracil (IC50=8.56 µg·mL−1). 相似文献
Quercetin, a naturally occurring potent antioxidant, is limited in therapeutic use, owing to its poor water solubility and stability. Herein, a method of conjugating quercetin to an aldehyde functionalized dextran via an HCl catalyzed condensation reaction to yield a water soluble quercetin functionalized polymer is reported. The prepared conjugate is characterized by 1H and 1H‐13C heteronuclear single quantum correlation (HSQC) NMR, which demonstrate that conjugation occurs via both the A‐ and B‐rings of quercetin. The degree of quercetin functionalization can be tuned by varying the reaction temperature and/or the concentration of the HCl catalyst. However, as temperatures and HCl concentrations are increased above 40 °C and 2 m , respectively, the increase in functionalization is accompanied by an increase in the oxidation of the conjugated quercetin and a decrease in polymer yield. The prepared conjugate is shown to have improved stability compared with native quercetin while maintaining substantial free‐radical scavenging activity. Anticancer activity is evaluated in vitro in a neuroblastoma cell line. The dextran–aldehyde–quercetin conjugate prepared at 40 °C and 2 m HCl is shown to be cytotoxic to neuroblastoma cells (SH‐SY5Y–IC50 = 123 µg mL−1 and BE(2)‐C–IC50 = 380 µg mL−1) but shows no activity against nonmalignant MRC‐5 cells at concentrations up to 400 µg mL−1. 相似文献
The synthesis of potassium (η2‐4‐allyl‐2‐methoxyphenol)trichloridoplatinate(II), K[PtCl3(C10H12O2)], ( 1 ), starting from Zeise's salt and Ocimum sanctum L. oil has been optimized. Starting from ( 1 ), three new platinum(II) complexes, namely (η2‐4‐allyl‐2‐methoxyphenol)chlorido(2‐methylquinolin‐8‐olato‐κ2N ,O )platinum(II), ( 2 ), (η2‐4‐allyl‐2‐methoxyphenol)chlorido(5‐nitroquinolin‐8‐olato‐κ2N ,O )platinum(II), ( 3 ), and (η2‐4‐allyl‐2‐methoxyphenol)chlorido(5,7‐dichloroquinolin‐8‐olato‐κ2N ,O )platinum(II), [Pt(C9H4Cl2NO)Cl(C10H12O2)], ( 4 ), containing eugenol and a quinolin‐8‐ol derivative (R‐OQ), have been synthesized and characterized by elemental analyses, MS, IR, 1H NMR and NOESY spectra. For ( 1 ) and ( 4 ), single‐crystal X‐ray diffraction studies were also carried out. Complexes ( 2 )–( 4 ) show good inhibiting abilities on three human cancer cell lines, i.e. KB, Hep‐G2 and LU, with IC50 values of 1.42–17.8 µM . Complex ( 3 ) gives an impressively high activity against KB, Hep‐G2, LU and MCF‐7, with IC50 values of 1.42–4.91 µM , which are much lower than those of cisplatin and some other platinum(II) complexes. 相似文献
Transition‐metal complexes bearing fluorinated phosphane and thiolate ligands has been an area of study in recent years and the chemical context of the current work is related to the metal‐assisted functionalization of fluorinated derivatives. The cis and trans isomers of the square‐planar complex bis[(pentafluorophenyl)diphenylphosphane‐κP]bis(2,3,5,6‐tetrafluorobenzenethiolato‐κS)platinum(II), [Pt(C6HF4S)2{P(C6H5)2(C6F5)}2], have been crystallized from a single chromatographic fraction and characterized by X‐ray diffraction analysis. The stabilization of the cis isomer results from weak intramolecular π‐stacking interactions and possibly from the formation of a C—F…Pt contact, characterized by an F…Pt separation of 2.957 (6) Å. The natural bond orbital analysis (NBO) for this isomer confirms that the corresponding F → Pt charge transfer accounts for 6.92 kcal mol−1 in the isomer stabilization. Such interactions are not present in the centrosymmetric trans isomer. 相似文献
Poly(amidoamine)s with amino pendant groups were prepared by hydrogen‐transfer polyaddition of primary and secondary amines to bis‐acrylamines. Dansyl cadaverine (DC) doxorubicin (Dox) were bound to the polymers via a cis‐aconityl spacer to give conjugates containing 3 µg of DC per mg of polymer and 28 to 35 µg of Dox per mg of polymer. Release of DC and Dox at physiological and acidic pH varied from 0 to 35% over 48 h and was pH dependent. Although the ISA1Dox conjugate (IC50 = 6 µg Dox · mL?1) presented similar toxicity as the parent polymer without Dox, ISA23Dox showed increased toxicity (IC50 = 10 µg Dox · mL?1). These results suggest that ISA23Dox is able to release biologically active Dox in vitro and that this conjugate might be suitable for further development.
The reaction of silver acetate with cis-[PtI2(dbtp)2], where dbtp = 5,7-ditertbutyl-1,2,4-triazolo-[1,5-a]pyrimidine, yielded cis-[Pt(OOCCH3)2(dbtp)2]·dmf (1). The complex has been analyzed by multinuclear magnetic resonance (1H, 13C, 15N), IR, and Raman. The compound formed two rotamers in CDCl3 and its spatial structures have been optimized using computational calculation. It was found that head-to-tail rotamer (1a) is more stable than its head-to-head counterpart (1b). In vitro antiproliferative activity against four tumor cell lines (A549, T47D, FaDu, and A2780cis) revealed in all cases significant cytotoxicity (IC50 = 0.26–1.80 μM), possessing IC50 values at least fivefold lower than cisplatin, carboplatin, and oxaliplatin (except A2780cis). The remarkable in vitro activity against T47D and A2780cis suggested the ability to overcome cisplatin resistance in these types of tumor cells. In addition, in vitro toxicity was evaluated against BALB/3T3 and has shown that the lipophilic platinum(II) complex (1) inhibits cell proliferation weaker than cisplatin and oxaliplatin. Additionally, cis-[Pt(OOCCH3)2(dbtp)2]·dmf exhibited selective activity, in contrast to cisplatin or oxaliplatin. 相似文献
The syntheses and structures of two mixed‐ligand complexes of platinum(II) with deprotonated oxopurine bases and triphenylphosphine are reported, namely the theophyllinate complex cis‐bis(1,2,3,6‐tetrahydro‐1,3‐dimethylpurine‐2,6‐dionato‐κN7)bis(triphenylphosphine‐κP)platinum(II), [Pt(C7H7N4O2)2(C18H15P)2], (I), and the theobrominate complex cis‐chloro(1,2,3,6‐tetrahydro‐3,7‐dimethylpurine‐2,6‐dionato‐κN1)bis(triphenylphosphine‐κP)platinum(II) ethanol hemisolvate, [PtCl(C7H7N4O2)(C18H15P)2]·0.5C2H5OH, (II). In (I), the coordination geometry of Pt is square planar, formed by the two coordinating N atoms of the theophyllinate anions in a cis arrangement and two P atoms from the triphenylphosphine groups. In (II), there are two crystallographically independent molecules. They both exhibit a square‐planar coordination geometry around Pt involving one Cl atom, the coordinating N atom of the theobrominate anion and two P atoms from the triphenylphosphine groups. The two triphenylphosphine groups are arranged in a cis configuration in both structures. The heterocyclic rings are rotated with respect to the coordination plane of the metal by 82.99 (8) and 88.09 (8)° in complex (I), and by 85.91 (16) and 88.14 (18)° in complex (II). Both structures are stabilized by intramolecular stacking interactions involving the purine rings and the phenyl rings of adjacent triphenylphosphine moieties. 相似文献
We combine nanotechnology and chemical synthesis to create a novel multifunctional platinum drug delivery vehicle based on magnetic carbon nanotubes (multiwall carbon nanotubes/Fe3O4@poly(citric acid)/cis‐[(Pt(1,7‐phenanthroline)(DMSO)Cl2)]‐b‐poly(ethylene glycol) (MCNTs/FO@PC/Pt(II)‐b‐PEG)) for targeted cancer therapy. MCNTs/FO@PC/Pt(II)‐b‐PEG was conveniently prepared by conjugating cis‐[Pt(1,7‐phenanthroline)(DMSO)Cl2] complex to MCNTs/FO@PC‐b‐PEG via strong hydrogen‐bonding interactions. In comparison with free cisplatin and Pt(II) complex, MCNTs/FO@PC/Pt(II)‐b‐PEG shows higher solubility in aqueous solution and higher cytotoxicity towards human cervical cancer HeLa cells and human breast cancer MDA‐MB‐231 cells. In vitro release experiments revealed that the platinum drug‐loaded delivery system is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but susceptible to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of loaded drugs. Fluorescence microscopy studies revealed that this magnetic nanohybrid system possesses marked cell‐specific targeting in vitro in the presence of an external magnetic field. The results indicated that the prepared superparamagnetic MCNTs/FO@PC/Pt(II)‐b‐PEG nanohybrid system is a promising candidate for inhibiting the proliferation of cancer cells. 相似文献
The electrochemical, UV/Vis–NIR absorption, and emission‐spectroscopic features of (TBA+)( 1 −) and the corresponding neutral complex 1 were investigated (TBA+=tetrabutylammonium; 1 −=[AuIII(Pyr,H‐edt)2]−; Pyr,H‐edt2−=pyren‐1‐yl‐ethylene‐1,2‐dithiolato). The intense electrochromic NIR absorption (λmax=1432 nm; ε=13000 M −1 cm−1 in CH2Cl2) and the potential‐controlled visible emission in the range 400–500 nm, the energy of which depends on the charge of the complex, were interpreted on the grounds of time‐dependent DFT calculations carried out on the cis and trans isomers of 1 , 1 −, and 1 2−. In addition, to evaluate the nonlinear optical properties of 1 x− (x=0, 1), first static hyperpolarizability values βtot were calculated (βtot=78×10−30 and 212×10−30 esu for the cis isomer of 1 − and 1 , respectively) and compared to those of differently substituted [Au(Ar,H‐edt)2]x− gold dithiolenes [Ar=naphth‐2‐yl ( 2 ), phenyl ( 3 ); x=0, 1]. 相似文献
Abstract A flow‐injection spectrophotometric procedure was developed for determining N‐acetylcysteine in pharmaceutical formulations. The sample was dissolved in deionized water and 400 µl of the solution was injected into a carrier stream of 1.0×10?2 mol l?1 sodium borate solution. The sample flowed through a column (70 mm length×2.0 mm i.d.) packed with Zn3(PO4)2 immobilized in a polymeric matrix of polyester resin and Zn(II) ions were released from the solid‐phase reactor because of the formation of the Zn(II) (N‐acetylcysteine)2 complex. The mixture merged with a stream of borate buffer solution (pH 9.0) containing 5.0×10?4 mol l?1 Alizarin red S and the Zn(II)Alizarin red complex formed was measured spectrophotometrically at 540 nm. The analytical curve was linear in the N‐acetylcysteine concentration range from 3.0×10?5 to 1.5×10?4 mol l?1 (4.9 to 24.5 µg ml?1) with a detections limit of 8.0×10?6 mol l?1 (1.3 µg ml?1). The relative standard deviations (RSDs) were smaller than 0.5% (n=10) for solutions containing 5.0×10?5 mol l?1 (8.0 µg ml?1) and 8.0×10?5 mol l?1 (13.0 µg ml?1) of N‐acetylcysteine, and the analytical frequency was 60 determinations per hour. A paired t‐test showed that all results obtained for N‐acetylcysteine in commercial formulations using the proposed flow‐injection procedure and a comparative procedure agreed at the 95% confidence level. 相似文献
[Pt(cur)(NH3)2](NO3) ( 1 ), a curcumin‐bound cis‐diammineplatinum(II) complex, nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases photoactive curcumin and an active platinum(II) species upon irradiation with visible light. The hydrolytic instability of free curcumin reduces upon binding to platinum(II). Interactions of 1 with 5′‐GMP and ct‐DNA indicated formation of platinum‐bound DNA adducts upon exposure to visible light (λ=400–700 nm). It showed apoptotic photocytotoxicity in cancer cells (IC50≈15 μM ), thus forming ?OH, while remaining passive in the darkness (IC50>200 μM ). A comet assay and platinum estimation suggest Pt–DNA crosslink formation. The fluorescence microscopic images showed cytosolic localization of curcumin, thus implying possibility of dual action as a chemo‐ and phototherapeutic agent. 相似文献