Structure–antimicrobial activity of some natural isocoumarins and their analogues

Three naturally occurring isocoumarins (paepalantine, paepalantine 9-O-beta-D-glucopyranoside and paepalantine 9-O-beta-D-allopyranosyl(1 --> 6) glucopyranoside) and two semi-synthetic analogues, 9,10-acylated compound and 9-OH-10-methylated compound, structurally similar to paepalantine, were evaluated for antimicrobial activity using a spectrophotometric microdilution technique. The paepalantine was active against S. aureus, S. epidermidis, and E. faecalis while the other four compounds proved ineffective against all microorganisms tested at concentrations of 500 microg/ml. Variations in phenolic substitution at OH-9 and/or OH-10 in the paepalantine molecule resulted in compounds without antimicrobial activity. A combination of structural features, two phenolic groups as cathecolic system, forms an oxygenated system arrangement that may reflect the potentially antimicrobial properties of paepalantine.     

High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis

1. Download : Download high-res image (99KB)
2. Download : Download full-size image

     

Structure of Cu2(indomethacin)4 and the reaction with superoxide in aprotic systems

The copper complex of indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole acetate), a common anti-inflammatory drug, was prepared and characterized. Crystal structure determination revealed the dimeric form of the 1:2 complex, namely Cu₂(indomethacin)₄ · L₂, in the unit cell. Suprisingly, the copper-copper distance (263 pm) was very close to metallic copper (256 pm). The two coordination sites in the copper-copper axis can be readily replaced by superoxide. An intriguing similarity to Cu₂(acetate)₄ was seen.Due to the lipophilic nature of the indomethacin ligand, this copper complex reacted with superoxide in aprotic solvents. The superoxide dismutating activity was successfully demonstrated in Me₂SO/water and acetonitrile/water mixtures using the nitro-blue tetrazolium assay and pulse radiolysis. The second-order rate constant of 6 · 10⁹ M^?1 · s^?1 in strictly aqueous systems dropped only slightly to 1.1 · 10⁹ M^?1 · s^?1 when aprotic solvents were used. This is the fastest rate constant ever observed for a copper-dependent dismutation of superoxide. The KO₂-induced lipid peroxidation in both erythrocytes and liver microsomes was suppressed by 70% in the presence of 1 · 10^?10 mol · ml^?1 of Cu₂(indomethacin)₄. The inhibitory action dropped to 25% when Cu₂Zn₂superoxide dismutase was employed. The formation of copper · indomethacin in rat serum after administration of indomethacin was shown in vitro and in vivo.     

Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC₅₀ values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC₅₀ > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.     

Current and emerging commercial optical biosensors.

The field of commercial optical biosensors is rapidly evolving, with new systems and detection methods being developed each year. This review outlines the currently available biosensor hardware and highlights unique features of each platform. Affinity-based biosensor technology, with its high sensitivity, wide versatility and high throughput, is playing a significant role in basic research, pharmaceutical development, and the food and environmental sciences. Likewise, the increasing popularity of biosensors is prompting manufacturers to develop new instrumentation for dedicated applications. We provide a preview of some of the emerging commercial systems that are dedicated to drug discovery, proteomics, clinical diagnostics and routine biomolecular interaction analysis.     

Preparation and Evaluation of Differently Sulfonated Styrene–Divinylbenzene Cross-linked Copolymer Cationic Exchange Resins as Novel Carriers for Drug Delivery

The differently sulfonated styrene–divinylbenzene cross-linked copolymer cationic exchange resins were prepared by oil-in-water polymerization and varied degrees of sulfonation. Several characteristics of the obtained resins were evaluated, i.e., Fourier transform infrared spectra, the ion-exchange capacity, microscopic morphology, size, and swelling. The resin characteristics were altered in relation to the degree of sulfonation, proving that differently sulfonated resins could be prepared. The behavior of chlorpheniramine (CPM) loading and in vitro release in the USP simulated gastric (SGF) and intestinal fluids (SIF) of the obtained resins were also evaluated. The CPM loaded in the resinates (drug-loaded resins) increased with the increasing degree of sulfonic group and hence the drug binding site in the employed resins. The CPM release was lower from the resins with the higher degree of sulfonic group due to the increase in the diffusive path depth. The CPM release was obviously lower in SGF than SIF because CPM, a weak base drug, ionized to a greater extent in SGF and then preferred binding with rather than releasing from the resins. In conclusion, the differently sulfonated resins could be utilized as novel carriers for drug delivery.     

多种天敌控制多种害虫的模糊数学模型

从生态经济学的原理出发，利用模糊集理论，探讨如何评价天敌控制多种害虫的为害作用，提出了多种天敌控制多种害虫的模糊数学模型。同时又得到了天敌对害虫的控制能力C，影响率G，影响强度H，及权数ω(x)的计算公式，以及在天敌作用下安全度的讨论与分析。     

Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Variation of chemical composition and antioxidant activity of essential oils of Mentha x rotundifolia (L.) Huds. (Lamiaceae) collected from different bioclimatic areas of Tunisia

The variation of the essential oils composition of 10 Tunisian Mentha x rotundifolia (L.) Huds. Populations and their antioxidant activity were assessed. Essential oils showed high percentages of oxygenated monoterpenes and sesquiterpene hydrocarbons. Rotundifolone, p-menthane-1,2,3-triol, β-caryophyllene and germacrene D were identified as main compounds at the species level. A variation in the essential oil composition was observed according to the populations and ecological factors. The populations 7, 8, 9 and 10 from the upper semi-arid bioclimatic zone and situated at high altitudes, exhibited the highest amount of rotundifolone. The populations 1, 2, 3, 4 and 5 from the lower humid showed a rotundifolone/β-caryophyllene/germacrene D chemotype. The population 6, situated at the lowest altitude, was characterized by the highest amount of p-menthane-1,2,3-triol. The level of antioxidant activity of the populations was linked to their chemical composition difference. The highest scavenging activity and the best ability to reduce ferric ions were recorded for the population 10. The most important capacity to inhibit β-carotene bleaching was revealed for the population 8. For all populations, the antioxidant activities were substantial but lower than antioxidant standards used (Trolox and BHT).The populations (7, 8, 9 and 10) from the upper semi-arid showed the best yields of essential oils and the highest contents of rotundifolone. Chemotypes within these populations could be selected for improvement programs.