The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.     

A microfluidic chip‐based fluorescent biosensor for the sensitive and specific detection of label‐free single‐base mismatch via magnetic beads‐based “sandwich” hybridization strategy

A novel microfluidic chip‐based fluorescent DNA biosensor, which utilized the electrophoretic driving mode and magnetic beads‐based “sandwich” hybridization strategy, was developed for the sensitive and ultra‐specific detection of single‐base mismatch DNA in this study. In comparison with previous biosensors, the proposed DNA biosensor has much more robust resistibility to the complex matrix of real saliva and serum samples, shorter analysis time, and much higher discrimination ability for the detection of single‐base mismatch. These features, as well as its easiness of fabrication, operation convenience, stability, better reusability, and low cost, make it a promising alternative to the SNPs genotyping/detection in clinical diagnosis. By using the biosensor, we have successfully determined oral cancer‐related DNA in saliva and serum samples without sample labeling and any preseparation or dilution with a detection limit of 5.6 × 10^?11 M, a RSD (n = 5) < 5% and a discrimination factor of 3.58–4.54 for one‐base mismatch.     

Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture

The capture of circulating tumor cells (CTCs) from cancer patient blood enables early clinical assessment as well as genetic and pharmacological evaluation of cancer and metastasis. Although there have been many microfluidic immunocapture and electrokinetic techniques developed for isolating rare cancer cells, these techniques are often limited by a capture performance tradeoff between high efficiency and high purity. We present the characterization of shear‐dependent cancer cell capture in a novel hybrid DEP–immunocapture system consisting of interdigitated electrodes fabricated in a Hele‐Shaw flow cell that was functionalized with a monoclonal antibody, J591, which is highly specific to prostate‐specific membrane antigen expressing prostate cancer cells. We measured the positive and negative DEP response of a prostate cancer cell line, LNCaP, as a function of applied electric field frequency, and showed that DEP can control capture performance by promoting or preventing cell interactions with immunocapture surfaces, depending on the sign and magnitude of the applied DEP force, as well as on the local shear stress experienced by cells flowing in the device. This work demonstrates that DEP and immunocapture techniques can work synergistically to improve cell capture performance, and it will aid in the design of future hybrid DEP–immunocapture systems for high‐efficiency CTC capture with enhanced purity.     

Formation of Glyco-Functionalized Platinum Complexes by Cross-Metathesis and Evaluation of Their Efficacy in Inhibition of Lung Tumor Cell Lines

Syntheses of carbohydrate-functionalized platinum complexes resembling presently employed cytostatics were performed. Mono-allylated sugar substrates obtained in two steps from glucose and galactose were connected with 2-allyl diethyl malonate by cross-metathesis. Following hydrogenation and acidic cleavage of the ester and alkylidene functionalities gave dicarboxylated glycoconjugates, which were transformed into their diammine platinum complexes. The antitumor activities of these platinum complexes were checked by sensitivity testing with 11 lung cancer cell lines. The novel glucose-platinum complex proved to be comparable to the drug carboplatin.     

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Two new prodrugs, bearing two and three 5‐fluorouracil (5‐FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5‐FU, they were intended to form complexes through H‐bonds to an organo‐bridged silane prior to hydrolysis‐condensation through sol–gel processes to construct acid‐responsive bridged silsesquioxanes (BS). Whereas 5‐FU itself and the prodrug bearing two 5‐FU units completely leached out from the corresponding materials, the prodrug bearing three 5‐FU units was successfully maintained in the resulting BS. Solid‐state NMR (²⁹Si and ¹³C) spectroscopy show that the organic fragments of the organo‐bridged silane are retained in the hybrid through covalent bonding and the ¹H NMR spectroscopic analysis provides evidence for the hydrogen‐bonding interactions between the prodrug bearing three 5‐FU units and the triazine‐based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and ¹³C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5‐FU thanks to a controlled and targeted drug delivery.     

Multifunctional Core‐Shell‐Corona‐Type Polymeric Micelles for Anticancer Drug‐Delivery and Imaging

We have developed core‐shell‐corona‐type polymeric micelles that can integrate multiple functions in one system, including the capability of accommodating hydrophobic dyes into core and hydrophilic drug into the shell, as well as pH‐triggered drug‐release. The neutral and hydrophilic corona sterically stabilizes the multifunctional polymeric micelles in aqueous solution. The mineralization of calcium phosphate (CaP) on the PAA domain not only enhances the diagnostic efficacy of organic dyes, but also works as a diffusion barrier for the controlled release.     

Near‐Infrared‐Controlled,Targeted Hydrophobic Drug‐Delivery System for Synergistic Cancer Therapy

Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near‐infrared (NIR)‐regulated hydrophobic drug‐delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin‐loaded AuMP‐polyethylene glycol‐folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote‐controlled hydrophobic drug‐delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR‐controlled, targeted drug‐delivery method would promote the development of high‐performance hydrophobic anticancer drug‐delivery system in future clinical applications.     

Editorial Board: Electrophoresis 10'14

Electrophoresis 2014, 35, 1504–1508. DOI: 10.1002/elps.201400001 Combination of DNA biobarcode assay with micro‐capillary electrophoretic analysis on a chip allows us to perform breast and colorectal cancer cell detection with high sensitivity, multiplexity, and accuracy.

     

载紫杉醇星型M-PLA-TPGS纳米颗粒的合成及其用于前列腺癌治疗药物载体的研究

合成了一种甘露醇引发的星型共聚物甘露醇-聚乳酸-聚乙三醇1000维生素E琥珀酸酯(M-PLATPGS).利用纳米沉淀法制备载紫杉醇M-PLA-TPGS纳米颗粒.纳米颗粒近似球形,粒径分布较窄.对载药纳米颗粒进行粒径、表面电荷、载药量、包封率和体外药物释放的表征,结果表明,体外药物释放呈双相释放模型,M-PLA-TPGS纳米颗粒在前列腺癌PC-3细胞中的摄取水平要高于PLGA和PLA-TPGS纳米颗粒.载紫杉醇M-PLA-TPGS纳米颗粒对于前列腺癌细胞的的毒性显著高于载紫杉醇PLA-TPGS纳米颗粒和商业制剂Taxol,证明星型M-PLA-TPGS聚合物作为纳米药物载体优于线性PLGA和PLA-TPGS聚合物.