Synthesis of new bicarbazole-linked triazoles as non-cytotoxic reactive oxygen species (ROS) inhibitors

Abstract

Carbazole analogs 3 and 4 and a new library of bicarbazole-linked triazoles 6–11 were prepared via new synthetic methodology. Metal-catalyzed oxidative coupling reaction was utilized for the synthesis of bicarbazole acetylene 4 and different metals (Zn⁺², Co⁺², Fe⁺³, Ni⁺², Cu⁺², Mn⁺²) as catalyst were screened. Only Fe-catalyzed reaction was found to be excellent and gave homocoupled product 4. Cu-catalyzed 1,3-dipolar cycloaddition was also utilized to install triazole moiety for the synthesis of hybrid molecules 6–11. Based on reported anti-inflammatory activity of carbazole and triazole scaffolds, all compounds were screened for their reactive oxygen species (ROS) inhibitory potential. Results from these studies revealed triazole 9 as most active compound (IC₅₀ value of 7.6?±?0.1?µg/mL on human whole blood and 2.7?±?0.09?µg/mL on isolated neutrophils) using ibuprofen as a standard. Therefore, class described herein can serve as attractive structural element for further studies on ROS inhibition.     

Determination of Cobalt(II)-Hydrogen Peroxide-Induced DNA Oxidative Damage and Preventive Antioxidant Activity by CUPRAC Colorimetry

Abstract

The classical Fenton system composed of Fe(II) and H₂O₂ uses harsh oxidative conditions and cannot realistically simulate physiological oxidations which are less severe. Here, reactive oxygen species (ROS) were generated with a combination of CoSO₄ and H₂O₂ to provide milder conditions. DNA was used as a biologically meaningful probe for monitoring the oxidative conversion. Oxidative hazard on DNA was accomplished in ammonia/ammonium chloride buffer at 37?°C, and the Fenton reaction was stopped with trichloroacetic acid (TCA). A suitable aliquot of this solution was added to cupric ion reducing antioxidant capacity (CUPRAC) reaction mixture, and the absorbance at 450?nm was recorded. The oxidized species derived from DNA were CUPRAC-reactive while intact DNA was not. The protective effects of antioxidants (AOxs), known to have radical scavenging effects, were tested; green tea and a synthetic fetal bovine serum (FBS) were also successfully used as real ROS scavengers. Although the classical iron-based Fenton procedure applied in ethanol medium generated CUPRAC-responsive products, the proposed system was perfectly ethanol-tolerant, enabling the CUPRAC measurement of DNA oxidation products against an unaffected reagent blank. The protective effects of phenolic antioxidants, perfectly solubilized in ethanol, could also be measured.     

Analysis of Silver Nanoparticles Using Single-Particle Inductively Coupled Plasma – Mass Spectrometry (ICP-MS): Parameters Affecting the Quality of Results

Single–particle analysis using inductively coupled plasma mass spectrometry offers a new tool for the characterisation of inorganic nanoparticles. Its development is connected with new generations of ultrafast spectrometers. This work is concerned with thorough investigation of parameters affecting the quality of the analysis of Ag nanoparticles, i.e., nanoparticle stability, transport efficiency and sensitivity of determination. The short-term stability of Ag nanoparticles in demineralised water can be prolonged to at least 7?h by the addition of 0.05% gelatin. The sensitivity was affected by plasma power and the nebuliser Ar flow. The transport efficiency decreased with increasing sample uptake, so a compromise between the efficiency and the total number of particles entering the spectrometer should be selected. The estimate of transport efficiency is distorted when more concentrated dispersions of nanoparticles are analysed because of the overlapping of signals of multiple nanoparticles. This effect was observed for dispersions of concentration greater than 1?×?10⁶?mL^?1 where an apparent decrease in transport efficiency from an initial value 7–8% to 1% was observed. The following parameters were found by method validation: concentration limit of detection of 97?mL^?1, nanoparticle diameter limit of detection 15?nm, linearity from 20 to at least 100?nm and repeatability of 1.3%. After validation, the method was applied to determine Ag nanoparticles in river water from the Vltava in Prague. Nanoparticles with diameters of 32–114?nm were found, and their number concentration increased from 340?mL^?1 to 1670?mL^?1 as the stream of water passed through urban agglomeration.     

Silver Nanostructures on Graphene Oxide as the Substrate for Surface-Enhanced Raman Scattering (SERS)

Nanosized surface-enhanced Raman scattering (SERS) substrates fabricated by the controlled growth of metal nanostructures on water-dispersed two-dimensional nanomaterials can open a new avenue for SERS analysis of liquid samples in biological fields. In this work, regular and uniform Ag nanostructures were grown on the surface of graphene oxide (GO) through a microwave-assisted hydrothermal method. Polyamidoamine (PAMAM) dendrimers were assembled on the surface of GO to form GO/PAMAM templates for growing Ag nanostructures, which are primarily comprised of Ag dimers and trimers. The prepared Ag/GO nanocomposites are highly dispersed and stable in aqueous solution and may be used as substrates for enhanced Raman detection of rhodamine 6?G (R6G) in aqueous solution. This special substrate provides high-performance SERS and suppresses R6G fluorescence in aqueous solution and is promising as a nanosized material for the enhanced Raman detection of liquid samples in biological diagnostics.     

Azadirachta indica leaves mediated green synthesized copper oxide nanoparticles induce apoptosis through activation of TNF-α and caspases signaling pathway against cancer cells

Green nanotechnology elucidates highly prioritized anticancer activity. We synthesized Copper oxide nanoparticles (CuONPs) using leaves of Azadirachta indica (A. indica) plants and studied the molecular mechanism of cancer cell apoptosis. After their synthesis, with the help of expository tools like Fourier transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), Dynamic light scattering (DLS) and surface zeta potential we confirmed the successful synthesis of CuONPs. Here, crystalline structure of green synthesized CuONPs of 36?±?8?nm size and spherical shape was able to kill MCF-7 and Hela cells, estimated by MTT assay. Successful internalization of Cu⁺² ions inside the cell was estimated by the atomic absorption study. Cellular uptake of Cu⁺² ions inflicted significant Reactive Oxygen Species (ROS) generation inside the cancer cells, thereby leading to DNA fragmentation as observed by DAPI staining. In in vivo model, CuONPs reduced the breast tumor volume in Balb/C mice and increased the mean survival time through the alteration of pro-inflammatory cytokines level. In case of both in vivo and in vitro models, CuONPs altered the pro-inflammatory cytokine level and pro-apoptotic protein expressions. In future, green synthesized CuONPs might be beneficial for its application as an anticancer drug in in vivo (mice model) and in vitro, though further study is needed on its toxicity.     

Traditional uses,phytochemistry, pharmacology and other potential applications of Vitellaria paradoxa Gaertn. (Sapotaceae): A review

Vitellaria paradoxa Gaertn. is a multipurpose medicinal plant of the family Sapotaceae, and it has been widely used usually in the clinical traditional medicine as remedy for a wide range of diseases for several decades. In addition, the plant has also found applications in confectionery, cosmetics and soaps, and pharmaceuticals both locally and internationally. V. paradoxa, which has been identified with >150 phytoconstituents, is rich in oleanane-type triterpene acids and glycosides, such as paradoxosides A-E, tieghemelin A, parkiosides A-C, bassic acid, as well as flavonoids such as quercetin and catechin-type compounds. The extracts and the active constituents of V. paradoxa have been investigated for various pharmacological activities, including but not limited to anticancer, melanogenesis-inhibitory, antibacterial, anti-diabetic, antioxidant, anti-inflammatory, anti-diarrhoeal, and antifungal activities. Additionally, V. paradoxa has also been utilized in nanoparticles (NPs) synthesis. These NPs among other things have shown significant antinociceptive and antiedematogenic activities as well as environmental friendly adsorptive properties for the removal of pollutants from pharmaceutical effluents. Overall, this review comprehensively examines the traditional uses, phytochemistry, pharmacology, toxicology, clinical studies, and nanoparticles synthesized from V. paradoxa and their applications.     

Engineering nanostructures of CuO-based photocatalysts for water treatment: Current progress and future challenges

Nowadays, increasing extortions regarding environmental problems and energy scarcity have stuck the development and endurance of human society. The issue of inorganic and organic pollutants that exist in water from agricultural, domestic, and industrial activities has directed the development of advanced technologies to address the challenges of water scarcity efficiently. To solve this major issue, various scientists and researchers are looking for novel and effective technologies that can efficiently remove pollutants from wastewater. Nanoscale metal oxide materials have been proposed due to their distinctive size, physical and chemical properties along with promising applications. Cupric Oxide (CuO) is one of the most commonly used benchmark photocatalysts in photodegradation owing to the fact that they are cost-effective, non-toxic, and more efficient in absorption across a significant fraction of solar spectrum. In this review, we have summarized synthetic strategies of CuO fabrication, modification methods with applications for water treatment purposes. Moreover, an elaborative discussion on feasible strategies includes; binary and ternary heterojunction formation, Z-scheme based photocatalytic system, incorporation of rare earth/transition metal ions as dopants, and carbonaceous materials serving as a support system. The mechanistic insight inferring photo-induced charge separation and transfer, the functional reactive radical species involved in a photocatalytic reaction, have been successfully featured and examined. Finally, a conclusive remark regarding current studies and unresolved challenges related to CuO are put forth for future perspectives.