Platinum and ruthenium complexes as promising molecules in cancer therapy

Cancer is one of the most common fatal diseases in humans nowadays. About 20 million new cancer cases are expected in the next two decades worldwide. The development of new chemotherapeutic agents with improved properties is presently the main challenge in the medicinal chemistry. Cisplatin was introduced to oncology in 1978 as first chemotherapeutic agent regarding its specific interaction with DNA, leading to its damage and causing the cell death. Since the first application of cisplatin in cancer therapy, there has been a growing interest in new metal-based compounds, in particular platinum and ruthenium complexes, with better anticancer activity and less side-effects compared to cisplatin. Carboplatin and oxaliplatin have shown promising action against some types of cancer, which are resistant to cisplatin. With the aim to overcome cross-resistance to these Pt(II) drugs, bioavailable platinum complexes (satraplatin and picoplatin) firstly found application as orally administered drugs, as well as some combined therapies of Pt(II) drugs (cisplatin, picoplatin) with specific resistant modulators. In recent years, novel polymer and liposomal formulations of platinum drugs (prolindac, lipoplatin, lipoxal, aroplatin) have been designed with strategy to improve drug delivery to target cancer cells and reduce toxicity. Complexes based on ruthenium have great potential to become leading candidates for the medical use in anticancer therapy. Some of these compounds have shown good anticancer activity, both in vitro and in vivo and two of them (KP1019 and NAMI-A) have passed clinical trials and given promising results

The influence of diazinon and its metabolites on acetylcholinesterase, NA+/K+-ATPase and antioxidant enzymes in rat brain synaptosomes

The aim of this study was to investigate neurotoxic potential and oxidative stress responses of diazinon and its metabolites, diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol using synaptosomes as a model system. Synaptosomes were isolated from the brain of Wistar albino rats and incubated at 37oC for 1 hour in the presence of selected concentrations of the investigated compounds. Acetylcholinesterase, Na+/K+-ATPase and antioxidant enzymes activities were determined by standard spectrophotometric methods. Diazinon induced concentration-dependent acetylcholinesterase and Na+/K+-ATPase inhibition, while the activity of catalase, superoxide dismutase and glutathione peroxidase was not significantly affected. Increasing concentrations of diazoxon, oxo analog of diazinon, caused almost complete acetylcholinesterase and Na+/K+-ATPase inhibition, and activated antioxidant enzymes: catalase (up to 25%), superoxide dismutase (up to 55%) and glutathione peroxidase (up to 30%). Unlike diazoxon, diazinon hydrolysis product, 2-isopropyl-6-methyl-4-pyrimidinol did not remarkably change the activities of the investigated enzymes, except superoxide dismutase that was stimulated up to 25%. The obtained results suggest that neurotoxic and prooxidative potential of diazinon, thioorganophoshate used as a commercial insecticide preparation, significantly reinforces mostly due to its transformation to diazoxon in the metabolic pathways.Third International Conferenceon Radiation and Applications in Various Fields of Research, RAD 2015, June8-12, 2015, Budva, Montenegr

Influence of rhamnolipids, produced by Pseudomonas aeruginosa NCAIM(P), B001380 on Cr(VI) removal capacity in liquid medium

Pseudomonas aeruginosa NCAIM(P), B001380, a propitious bacterial strain isolated from mineral cutting oil was identified to be chromium tolerant and a producer of biosurfactant rhamnolipid (RL) with potential application in heavy metal bioremediation. Culture growth, RL production and Cr(VI) removal capacity of the strain in the presence of 50 mg L-1 (I) and 100 mg L-1 of Cr(VI) (II) were studied. Maximum of RL production were found in the late-stationary phase at 72 h for both Cr(VI)-amended cultures: I (236 mg L-1) and II (160 mg L-1), as well as the maximum of Cr(VI) removal capacity: 70 % (I) and 57 % (II). The amount of Cr in RL preparation II was 22 mg mg-1 determined by flame atomic absorption spectroscopy (FAAS). Appearance of a new band at 914 cm-1 in infrared (IR) spectrum of RL (II) indicated a significant proof for possible coordination of CrO42-ion with RL. The effect of Cr(VI) on monorhamnolipids (RL1) and dirhamnolipids (RL2) distribution and its ratio were studied by electrospray ionization mass spectrometry (ESI-MS). An increase was observed in a RL2/RL1 ratio for II compared to control

μ-1,2-Bis(diethyl­phosphino)ethane-κ2 P:P′-bis­{[1,2-bis­(diethyl­phosphino)ethane-κ2 P,P′]trichloridonitrosyl­tungsten(II)}

The title binuclear compound, [W2Cl6(NO)2(C10H22P2)3], contains two W atoms which are bridged by a bis­(diethyl­phosphino)­ethane (depe) ligand. The seven-coord­inated tungsten(II) centres display distorted penta­gonal–bipyramidal geometries with trans nitrosyl and chloride ligands. The title mol­ecule lies on a crystallographic inversion centre. The ethane group of the non-bridging depe ligand is positionally disordered, with site-occupancy factors of 0.63 and 0.37. In the crystal structure, the binuclear mol­ecules are linked by weak inter­molecular C—H⋯O and C—H⋯Cl inter­actions. In addition, weak intra­molecular C—H⋯Cl inter­actions are also present

Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy

Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review

trans-Bis[1,2-bis­(dimethyl­phosphino)­ethane]­bromido­nitrosyl­tungsten(0)

The crystal structure of the title compound, [WBr(NO)(C6H16P2)2], reveals a distorted octa­hedral geometry around the W centre. The W atom lies on a special position at an inversion centre (the Br and NO ligands are equally disordered). The bis­(dimethyl­phosphino)ethane ligand is also severely disordered (site occupancy factors 0.52 and 0.48). This is the first structure of a tungsten species with nitrosyl and bromide ligands

Chemical Composition, Total Phenols and Flavonoids Contents and Antioxidant Activity as Nutritive Potential of Roasted Hazelnut Skins (Corylus avellana L.)

The present study evaluates natural composition of Serbian roasted hazelnut skins (HS) with potential role in application as functional nutrient of various food products. Total phenols (TPC) and flavonoids contents (TFC) in HS extracts obtained with dierent ethanol concentrations (10%—I, 50%—II and 96%—III) and their antioxidant activities were investigated. The highest total phenols content (706.0 9.7 mgGAE/gextract) was observed in 96% ethanol HS extract. Ethanol HS extracts showed very high antioxidant activity with eective concentrations (EC50) ranged between 0.052 and 0.066 mg/mL. The phenol and flavonoid content of roasted HS extracts I–III was determined by HPLC-ESI-MS/MS analyses. Contents of lipids, proteins, carbohydrates, metals, and C, H, N, S elements in roasted HS were also determined. Relatively high C/N, C/P and C/N/P ratios, rich metal contents and fatty acids composition indicated that hazelnut skin might be a good candidate for use as either human or fungal functional nutrient. In addition, possible application of phenolic HS extracts as UV booster was studied by recording UV spectra (220–440 nm) of 10 mg/L of HS extracts I–III combined with 10 mg/L of chemical sunscreen agent benzophenone-3 and in vitro sun protection factor (SPF) was calculated

Bis[1,2-bis­(dimethyl­phosphino)­ethane]­dichloridonitro­syltungsten(0) chloride

In the crystal structure of the title compound, [WCl2(NO)(C6H16P2)2]Cl, the seven-coordinated tungsten(II) center displays a distorted penta­gonal–bipyramidal geometry with trans nitrosyl and chloride ligands. The NO and Cl ligands are disordered over two positions; the site occupancy factors are 0.6 and 0.4

The effects of diazinon and its degradation products on oxidative stress parameters in rat brain synaptosomes

In vitro evaluation of oxidative stress responses to various concentrations of diazinon and its degradation products, diazoxon and 2-isopropyl-6-methyl- 4-pyrimidinol (IMP) was investigated by determining antioxidant enzymes activity (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)) and lipid peroxidation level in rat brain synaptosomes. Diazinon showed negligible prooxidative properties causing increase in antioxidant enzymes activity and lipid peroxidation level up to 10%. Increasing concentrations of diazinon oxidation product, diazoxon activated CAT (up to 20%), SOD (up to 50%), GPx (up to 25%), and significantly increased the content of lipid peroxidation indicator (up to 50%). The investigated hydrolysis product of diazinon, IMP did not remarkably influence the activity of CAT, GPx and lipid peroxidation level (up to 10%), while it induced SOD stimulation up to 30%

In vitro evaluation of diazinon and its degradation products neurotoxicity potential in rat brain synaptosomes

Toxic effects of diazinon and its degradation products, diazoxon and 2- isopropyl-6-methyl-4-pyrimidinol (IMP), were investigated in vitro by determining the inhibition of acetylcholinesterase (AChE), Na+ /K+ -ATPase and ecto-ATPase activity in rat brain synaptosomes after 1 hour exposure toward varying concentrations. Dose-dependent AChE and Na+ /K+ -ATPase inhibition was obtained in the presence of diazinon, while diazinon concentrations below 0.1 mM did not noticeably affect ecto-ATPase activity. Diazinon oxidation product, diazoxon was found as the most toxic investigated compound. Diazoxon induced dose-dependent and almost complete inhibition of AChE, Na+ /K+ -ATPase and ecto-ATPase at the highest investigated concentration (0.1 mM), while hydrolysis product of diazinon, IMP did not remarkably influence their activities