Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer

Cyclin-dependent kinase 9 (CDK9) activity is correlated with worse outcomes of triple-negative breast cancer (TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction (PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CˆN ligand and tested their activity against the CDK9-cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Determination of UV-Vis Spectrophotometric Method of Metal Complexes Stoichiometry between Cu(II), Ca(II), Cd(II), Mg(II) and Zn(II) with Bupropion Hydrochloride

In this study, simple, rapid and accurate UV-Vis spectrophotometric method was developed for the determination ofcomplexes stoichiometry of Cu(II)-bupropion hydrochloride, Ca(II)-bupropion hydrochloride, Cd(II)-bupropionhydrochloride, Mg(II)-bupropion hydrochloride and Zn(II)-bupropion hydrochloride. The spectrums of the complexesformed between bupropion hydrochloride with Cu (II), Ca (II), Cd (II), Mg (II) and Zn (II) metal cations were taken in therange of 500 to 190 nm and the stoichiometry of the complexes formed between bupropion hydrochloride with Cu (II), Ca(II), Cd (II), Mg (II) and Zn (II) metal cations were determined by using the mole ratio method at maximum wavelength(λmax=252 nm). The stoichiometry of Cu(II)-bupropion hydrochloride, Ca(II)-bupropion hydrochloride, Cd(II)-bupropionhydrochloride and Zn(II)-bupropion hydrochloride were calculated as 1:1, but Mg(II)-bupropion hydrochloride complexwas calculated as 1:2. The recovery was found 95.0% for bupropion hydrochloride. Lambert-Beer’s obeyed theconcentration range of 1.40-6.91 µg/mL for bupropion hydrochloride. The LOD and LOQ were found to be 13.81 and 1.38µg/mL for bupropion hydrochloride, respectively. The interaction between bupropion hydrochloride with Cu (II), Ca (II), Cd(II), Mg (II) and Zn (II) were investigated by applying UV-visible spectrophotometric method, and satisfactory results wereobtained

Effect of Au(III) complex with oxymatrine and matrine on proliferation of tumor cells in vitro and its mechanisms / 中草药

Objective: To synthesize metal complexes of Au(III) with matrine (MT-Au) and oxymatrine (OMT-Au), compare their inhibitory effect on the proliferation of tumor cells in vitro, and discuss the mechanism and structure-activity relationship. Methods: The metal complexes were synthesized by solvothermal method and characterized by X-ray single crystal diffraction. The in vitro cytotoxicity of complexes with different doses towards 10 selected tumor cell lines was evaluated by MTT method. The effects of complex on cell apoptosis and cell cycle were investigated by flow cytometer. Agarose gel electrophoresis was used to study the effects of complex on topoisomerase I (TOPO I) activity. Results: Complex OMT-Au obviously inhibited the proliferation of MGC803 tumor cells, blocked cell cycle of MGC803 in G2/M phase, and suppressed TOPO I mediated untwisting of pUC19 DNA plasmid with a dose-dependence manner. And the inhibited effects of complex OMT-Au were all stronger than MT-Au complex. Conclusion: The antitumor activity of complex OMT-Au is stronger than that of MT-Au, which could be attributed to the variation in the molecular conformation of ligand.

Asymmetric oxidation synthesis of esomeprazole sodium:research advances / 国际药学研究杂志

Esomeprazole sodium is a widely used proton pump inhibitor which is mainly applied to the treatment of gastric ul-cer,duodenal ulcer,digestive esophagitis and gastritis. By reviewing the literature over the past decade on the asymmetric oxidation of esomeprazole sodium ,the paper summarizes the synthetic process and focuses on the comparison of the critical steps. To choose suit-able chiral catalyst to reduce the cost of synthesis of esomeprazole sodium,this paper compares beyond the yield,enantioselectivity and other aspects. The conclusion is that the catalysts used in the most of oxidation systems are with a large load and high cost ,and compared with the classical Kagan-Modena system,the Ti-salan catalyst has advantages in the synthesis of esomeprazole sodium,and can be widely used.

Study of the antimicrobial activity of metal complexes and their ligands through bioassays applied to plant extracts

The appearance of resistant bacteria was found to reduce the efficiency of antimicrobial therapies with the current antibiotics, thereby increasing the need for more efficient drugs for the treatment of infections. Several studies have demonstrated an increase in antimicrobial activity following the interaction of several compounds with metal ions. The present study used a methodology adapted for antimicrobial bioassays using plant extracts, in compliance with the standards of the Clinical and Laboratory Standards Institute against Gram-positive and Gram-negative bacteria. The results obtained were considered appropriate for determining MIC, MBC as for performing antimicrobial sensitivity testing with good efficiency and reproducibility. The bacteria Pseudomonas fluorescens exhibited high sensitivity to the tested compounds, being efficient to evaluate the antibacterial activity. The bioassays with the metal complexes of flavonoid quercetin and Ga(III) ions, and synthetic ligand H2bbppd and Cu(II) ions showed a greater inhibitory effect than their individual ligands, thus, the addition indicated an increase in the antimicrobial activity after the coordination. Both metal complexes exhibit good antimicrobial performances, such as low minimum inhibitory concentration (MIC ≤ 250 µg/ml), bactericidal effect and a broad activity spectrum, which qualify these compounds as suitable candidates to the next step of drugs fabrication. Nevertheless, further studies on the mechanism of growth inhibition and toxicity are needed, in order to evaluate the potential of therapeutic application.

Synthesis, characterization, and anti-cancer activity of emodin-Mn(II) metal complex / 中国天然药物

To synthesize and characterize a novel metal complex of Mn (II) with emodin, and evaluate its anti-cancer activity. The elemental analyses, IR, UV-vis, atomic absorption spectroscopy, TG-DSC, (1)H NMR, and (13)C NMR data were used to characterize the structure of the complex. The cytotoxicity of the complex against the human cancer cell lines HepG2, HeLa, MCF-7, B16, and MDA-MB-231 was tested by the MTT assay and flow cytometry. Emodin was coordinated with Mn(II) through the 9-C=O and 1-OH, and the general formula of the complex was Mn(II) (emodin)2·2H2O. In studies of the cytotoxicity, the complex exhibited significant activity, and the IC50 values of the complex against five cancer cell lines improved approximately three-fold compared with those of emodin. The complex could induce cell morphological changes, decrease the percentage of viability, and induce G0/G1 phase arrest and apoptosis in cancer cells. The coordination of emodin with Mn(II) can improve its anticancer activity, and the complex Mn(II) (emodin)2·2H2O could be studied further as a promising anticancer drug.

Study on the Preparation of Metal Complexes of Carboxymethyl Chitosan / 中国海洋药物

By complexation reaction with water-soluble carboxymethyl chitosan and Ca 2+ ?Fe 2+ ?Zn 2+ in solution,the metal complexes of Ca 2+ ?Fe 2+ ?Zn 2+ were preparated.The effects of various factors:reaction time,etmperature,substitution degree of carboxymethyl group,ionic strength and pH value on the reaction were investigated.The results showed that the optimum reaction condition was pH 5~7,time 10 min,the complex capacity of CMCS for metal ions increasing with the substitution degree of carboxymethyl group,decreasing with the ionic strength of solution.