Pyrimidine-derived disulfides as potential antimicrobial agents: synthesis and evaluation in vitro

Antibiotic resistance is a worldwide problem. The synthesis and evaluation of new antimicrobial compounds, without cytotoxicity against human cells, are highly desired. In this paper, the preparation of a class of pyrimidine-derived disulfides is described. Sulfenic acids were generated from suitable precursors and used as reactive intermediates that condensed with the thiol function of thiocytosine. An introductory study on the antimicrobial activity of this disulfide family is reported. Three family components, that revealed no cytotoxicity against human erythrocytes, exhibited inhibitory activity against Gram-positive Staphylococcus aureus.     

High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.     

Optimized protocol for the biocompatibility testing of compression stockings and similar products with close skin contact in vitro

Biocompatibility of six different compression stockings and cytotoxic effects were determined using HaCaT keratinocytes, L929 mouse fibroblasts, primary adult and juvenile keratinocytes Cells were quantified using a luminometric ATP assay and the photometric BCA test. Cytotoxic effects were determined by LDH release. An area-based extraction ratio of 1.25 cm²:mL could be shown to be superior to the weight-based extraction of test material. Extraction medium should be an acidic sweat solution as this helps to recreate in vivo conditions. Monolayer cultures of HaCaT keratinocytes or L929 mouse fibroblasts should be used for testing. Primary adult keratinocytes or primary juvenile keratinocytes can also be used. For the latter, testing under DMEM with FCS is recommended to achieve comparable results. It was found that the compression stockings tested exhibited no negative influence on cell viability in vitro and no direct cytotoxic effects measured as release of LDH. Hence, good biocompatibility could be asserted.     

Synthesis and biological activity of medium range molecular weight polymers containing exo‐3,6‐epoxy‐1,2,3,6‐tetrahydrophthalimidocaproic acid

A new monomer, exo‐3,6‐epoxy‐1,2,3,6‐tetrahydrophthalimidocaproic acid (ETCA), was prepared by reaction of maleimidocaproic acid and furan. The homopolymer of ETCA and its copolymers with acrylic acid (AA) or with vinyl acetate (VAc) were obtained by photopolymerizations using 2,2‐dimethoxy‐2‐phenylacetophenone as an initiator at 25 °C. The synthesized ETCA and its polymers were identified by FTIR, ¹H NMR and ¹³C NMR spectroscopies. The apparent average molecular weights and polydispersity indices determined by gel permeation chromatography (GPC) were as follows: M_n = 9600 g mol^?1, M_w = 9800 g mol^?1, M_w/M_n = 1.1 for poly(ETCA); M_n = 14 300 g mol^?1, M_w = 16 200 g mol^?1, M_w/M_n = 1.2 for poly(ETCA‐co‐AA); M_n = 17 900 g mol^?1, M_w = 18 300 g mol^?1, M_w/M_n = 1.1 for poly(ETCA‐co‐VAc). The in vitro cytotoxicity of the synthesized compounds against mouse mammary carcinoma and human histiocytic lymphoma cancer cell lines decreased in the following order: 5‐fluorouracil (5‐FU) ≥ ETCA > polymers. The in vivo antitumour activity of the polymers against Balb/C mice bearing sarcoma 180 tumour cells was greater than that of 5‐FU at all doses tested. © 2001 Society of Chemical Industry     

Synthesis,Biological Evaluation of 1,1‐Diarylethylenes as a Novel Class of Antimitotic Agents

The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B‐ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA‐4 ( 2 e ), isoCA‐4 ( 2 k ) and isoNH₂CA‐4 ( 2 s ) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC₅₀ values of 4, 2 and 1.5 μM , respectively. These derivatives were found to be 10‐fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G₂/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e , 2 k and 2 s on the vessel‐like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors.     

Comparison of additive effects on the PVA/starch cryogels: Synthesis,characterization, cytotoxicity,and genotoxicity studies

The research goal of this study is to produce suitable scaffolds for tissue engineering applications. Different ratios of polyvinyl alcohol (PVA)/starch (90:10, 70:30, 50:50) and crosslinking methods have been used to prepare cryogels. Chemically crosslinked cryogels were synthesized using glutaraldehyde as the crosslinking agent. For the physically crosslinked cryogels, sodium dodecyl sulfate was used during cryogelation as the foaming agent. Chemical structure and pore morphology were demonstrated by Fourier transform infrared spectroscopy and scanning electron microscopy (SEM). Swelling ratio and degradation profile of the scaffolds were also determined. 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay and SEM were used to investigate the biocompatibility of the scaffolds and cell morphology. Genotoxicity test was performed to show DNA fragmentation. The overall results demonstrated that PVA/starch cryogels could have potentially appealing application as scaffolds for tissue engineering applications and additives affect the architecture and characteristic properties of the cryogels.     

TiN／Ag多层膜的生物相容性研究

使用离子束辅助沉积（IBAD）的方法，在医用不锈钢317L的基底上制备TiN／Ag多层膜．在TiN／Ag多层膜具有良好的抗茵性和抗腐蚀性的研究基础上，通过细胞毒性试验和溶血试验评价了TiN／Ag多层膜的生物相容性．试验结果表明：TiN／Ag多层膜样品的细胞毒性等级在0～1之间；溶血率〈5％，符合生物医学材料的标准．这些说明TIN／Ag多层膜不仅具有抗菌性和抗腐蚀性，而且具有良好的生物相容性．     

Structural Effects on the Adhesive Properties of Butadiene/Styrene Radial Teleblock Copolymers

The effects of butadiene/styrene ratio, monomer distribution, and molecular weight distribution and branching on the pressure sensitive adhesive properties of butadiene/ styrene radial teleblock copolymers are reported. Styrene content of polymers with varying structures shows a close relation with tack response, and styrene content and structure affect solution viscosity and shear adhesion. When part of the styrene is incorporated into the polybutadiene segment to yield a block progressively enriched in styrene (tapered block), solution viscosity and shear adhesion are reduced. When the butadiene segment is replaced by a block of randomly copolymerized butadiene and styrene, the polymers provide lower solution viscosities and shear adhesion but unchanged tack.

The molecular weight distribution of the radial teleblock polymers can vary from broad, highly branched compositions to narrow molecular weight distributions of almost Iinear polymers. The latter have relatively high solution viscosity and low shear adhesion, whereas the former polymers produce moderate solution viscosity but high shear adhesion. Tack is generally unaffected.