Regioselective synthesis and initial evaluation of a folate receptor targeted rhaponticin prodrug

To improve the therapeutic effect of rhaponticin(RHA),a folate receptor(FR) targeted RHA prodrug was designed and regioselectively synthesized by utilizing a hydrophilic peptide spacer linked to folic acid(FA) via a releasable disulfide linker.A series of biological evaluation was investigated in vitro and in vivo.The positive results of biological investigations warrant further preclinical study before this novel targeted chemotherapeutic is considered for clinical investigation.     

Happy experience of a medical doctor curing from pancreatic cancer —A 60-day diary—

Pancreatic cancer was found by an abdominal CT scan in a medical doctor, the author of this article, before the appearance of any symptoms. After considering all the imaging findings including the CT, MRI, and PET, a diagnosis was made. He was admitted in the University of Tokyo Hospital on the 14th day after the CT finding. On the 18th day, the operation was successfully performed, and no tumor invading to adjacent tissue was seen. On the 29th day, 11th day after the operation, he left the hospital with a drain still in place to excrete abdominal exudation. The remaining drain was finally removed on the 60th day, and the treatment by the surgeon was completed. The chronological events that occurred during these 60 days are described in diary form. There is nothing superior to early detection and early treatment in the fight against cancer. He recommends everybody to receive periodical medical examinations before praying for good luck.     

Synthesis,characterization, and in vitro antioxidant and anticancer studies of ruthenium(III) complexes of symmetric and asymmetric tetradentate Schiff bases

Ruthenium(III) complexes of three tetradentate Schiff bases with N₂O₂ donors formulated as [RuCl(LL¹)(H₂O)], [RuCl(LL²)(H₂O)] and [RuCl(LL³)(H₂O)] were synthesized and characterized by elemental analyses, molar conductance, FTIR, and electronic spectral measurements. The FTIR data showed that the tetradentate Schiff base ligands coordinate to Ru ions through the azomethine nitrogen and enolic oxygen. The antioxidant activities of the complexes were investigated through scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. The DPPH activity for [RuCl(LL²)(H₂O)] with IC₅₀ = 0.031 mg mL^?1 was higher than the values obtained for the other Ru(III) compounds. The study revealed that the synthesized Ru(III) complexes of the tetradentate Schiff base exhibited strong scavenging activities against DPPH and moderate against ABTS radicals. In addition, the antiproliferative studies of the complexes were also tested against human renal cancer cells (TK10), human melanoma cancer cells (UACC62), and human breast cancer cells (MCF7) using the SRB assay. The results indicated that the Ru(III) complexes showed low anticancer activities against the tested human cancer cell lines.     

Synthesis,structure, and in vitro cytotoxicity of organoplatinum(II) complexes containing aryl olefins and quinolines

Ten new organoplatinum(II) complexes, [PtCl(Saf)(8-OQ)] (1), [Pt(Saf-1H)(8-OQ)] (2), [PtCl(Meug)(8-OQ)] (3), [Pt(Meug-1H)(8-OQ)] (4), [PtCl(Meteug)(8-OQ)] (5), [PtCl(Meteug)(Q)] (6), [Pt(Meteug)(Q-COO)] (7), [Pt(Eteug-1H)(Q)] (8), [Pt(Eteug-1H)(8-OQ)] (9), and [Pt(Eteug-1H)(Q-COO)] (10) (where Saf = safrole, Meug = methyleugenol, Meteug = methyl eugenoxyacetate, Eteug = ethyl eugenoxyacetate, Q = quinoline, 8-OQ = 8-hydroxyquinolinate, and Q-COO = quinolin-2-carboxylate), were synthesized and characterized by spectroscopic methods. The position of N and O donors of quinoline ligands in comparison with the ethylenic double bond and the aromatic C5 of the aryl olefins in platinum(II) coordination sphere of 1–10 was determined using their NOESY spectra and confirmed by single-crystal X-ray diffraction of 10. Complexes 1, 2, 3, 4, and 9 exhibit impressive activities on four human cancer cell lines KB, Hep-G2, Lu, and MCF7 with IC₅₀ = 1.4–9.6 μM. Complexes 1, 2, 4, and 9 gave better antitumor activity than cisplatin against examined cell lines.     

Determination of the Antineoplastic Agent Tiazofurin in Plasma by High Performance Liquid Chromatography

Abstract

A simple and sensitive sample clean up procedure and a reverse phase high performance liquid chromatographic assay for tiazofurin in dog plasma has been developed.

Thymidine was used as the internal standard and the elution solvent was 0.16 M acetic acid. The retention times of tiazofurin and thymidine at an elution rate of 2.0 ml/minute were 8.7 minutes and 16 minutes respectively. The assay sensitivity was 1.0 μG/ml. The within run coefficient of variation of 2.0 μG/ml and 20 μG/ml plasma samples were ±7.49% and ±3.37% respectively and the between run coefficient of variation of 2.0 μG/ml and 20.0 μG/ml plasma samples were ±10.46% and ±5.92% respectively.     

Synthesis of arotinoid acid and temarotene using mixed (Z)-1,2-bis(organylchalcogene)-1-alkene as precursor

An efficient and novel total synthesis of the two bioactive retinoids temarotene and arotinoid acid (TTNPB) is described. The key steps in this process include the regio and stereoselective hydrotelluration of thioacetylene 9 and Te/Li transmetalation of mixed (Z)-1,2-bis(organylchalcogene)-1-alkene (Z)-3. The subsequent reaction involving the β-phenylthio vinyl lithiated intermediate 10 with dimethyl sulfate gave the (E)-vinyl sulfide 11. The Ni⁺² cross-coupling of 11 with the corresponding phenylzinc bromide and p-oxazoline phenylzinc bromide 12 afforded the respective temarotene 2 and retinoid-oxazoline substituted 13. Finally, compound 13 was deprotected with HCl to furnish arotinoid acid (TTNPB) 1.     

动物肺吸虫病实验性化疗研究进展

总结了目前动物肺吸虫病的现状和实验性化疗研究进展,并对未来更有效的化疗提出展望。     

锇胺分子氢配合物的研究进展

由于锇胺分子氢配合物中有特殊的键M(η2 H2 )和特殊的配体 分子氢的存在 ,故而具有丰富的取代化学和特殊的光谱性质。在无机化学、配位化学、生物、医药等方面都有极为广阔的应用前景。本文就此进行了简要的回顾与展望     

Synthesis and Antiinflammatoryand Anticancer Activity Evaluation of Some Condensed Pyrimidines

Summary.  Upon condensation with 4-isothiocyanato-4-methyl-2-pentanone, 2,3-diaminonaphthalene and N-aminoethyladenosine gave in good yields substituted pyrimidonaphthoimidazole and imidazopyrimidine thione. Refluxing pyrimidobenzthiazole with methanol H₂SO₄ at pH∼1 resulted in S-methyl pyrimidobenzthiazole in moderate yield. Pyrimidobenzimidazole derivatives could be reacted to S-alkylated and N-acylated derivatives by refluxing with ethyl bromoacetate in the presence of anhydrous potassium carbonate in THF and by heating in an acetic acid/acetic anhydride mixture. Heating of pyrimidobenzimidazole with 75% aqueous H₂SO₄ on a water bath ended up in a rearranged product. All compounds gave correct ¹H NMR, IR, and HR mass spectra. Results of antiinflammatory, analgesic, and anticancer activity screening of the new compounds are described. Received October 29, 1999. Accepted (revised) January 13, 2000     

Molecular-scale drug delivery systems loaded with oxaliplatin for supramolecular chemotherapy

Smart strategies that can decrease the side effect and enhance the therapeutic efficacy of chemotherapy are in urgent need to meet the special demands of cance r therapy.Herein,two wate r-soluble macrocyclic hosts,i.e.,a carboxylated leaning tower[6]arene(CLT6) and a carboxylated [2]biphenyl-extended pillar[6]arene(CBpP6),are used to load chemotherapy drug oxaliplatin(OxPt) by forming inclusion complexes(OxPt■CLT6 and OxPt■CBpP6) through host-guest interactions.Interestingly,OxPt can be released from the macrocyclic cavities of these drug delivery systems(DDSs) via the competitive binding effect of spermine(SPM) because of the stronger binding abilities of CLT6/CBpP6 toward SPM as compared with OxPt,leading to enhanced cytotoxicity on SPM-overexpressed cancer cells,such as breast cancer MCF-7 cells.Moreover,compared to free OxPt,due to the low concentration of SPM in normal cells,OxPt■CGT6 and OxPt■CBpP6 demonstrated a decreased cytotoxicity on liver L02 cells,which is beneficial fo r reducing the side effect of anticancer drug during chemotherapy.Such a strategy might be extended to other antitumor drugs and water-soluble macrocycles with suitable cavity sizes to achieve controllable drug delivery and enhanced anticancer ability in supramolecular chemotherapy