Air-water interactions: The signature of meteorological and air-quality parameters on the chemical characteristics of water produced from the atmosphere.

Atmospheric water is considered an alternative sustainable solution for global water scarcity. We analyzed the effects of meteorological and air-quality parameters on the chemical characteristics of atmospheric water. First, we measured the chemical characteristics of water produced by a unique atmospheric water generator (AWG) apparatus in Tel Aviv, Israel. To examine the complex air-water relationships, we obtained atmospheric data from several sources: adjacent air-quality-monitoring stations, aerosol robotic network (AERONET), aerosol pollution profile using PollyXT lidar, and air back-trajectory simulation (HYSPLIT). We found a strong impact of different pollution sources on the water quality. The integration between HYSPLIT, AERONET and lidar analyses shows that the pathway crossed by the air parcel three days before arrival at the site affected the chemical properties of the produced water. Nearby sea salt aerosols from the Mediterranean were persistently observed in the water (medians: sodium 69 µg/L, chloride ions 120 µg/L), corresponding to lidar identification of a sea-breeze layer (30-50 sr lidar ratio in lower elevation). Seasonal variability in climatic conditions affected the concentration of dust-related elements in the water. During dust-storm events, calcium was the most dominant element (median 900 µg/L). Thus, the chemical characteristics of the water can be considered a "footprint" of both regional, local, and phenological composition of the atmosphere.

A Subset of New Platinum Antitumor Agents Kills Cells by a Multimodal Mechanism of Action Also Involving Changes in the Organization of the Microtubule Cytoskeleton.

The substitution inert platinum agent [Pt(1 S,2 S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]2+ (56MeSS, 5) is a potent cytotoxic metallodrug. In contrast to conventional cisplatin or oxaliplatin, the mechanism of action (MoA) of 5 is fundamentally different. However, details of the mechanism by which the 5,6-dimethyl-1,10-phenanthroline ligand contributes to the cytotoxicity of 5 and its derivatives have not been sufficiently clarified so far. Here, we show that 5 and its Pt(IV) derivatives exhibit an intriguing potency in the triple-negative breast cancer cells MDA-MB-231. Moreover, we show that the Pt(IV) derivatives of 5 act by multimodal MoA resulting in the global biological effects, that is, they damage nuclear DNA, reduce the mitochondrial membrane potential, induce the epigenetic processes, and last but not least, the data provide evidence that changes in the organization of cytoskeleton networks are functionally important for 5 and its derivatives, in contrast to clinically used platinum cytostatics, to kill cancer cells.

Triple action Pt(iv) derivatives of cisplatin: a new class of potent anticancer agents that overcome resistance.

A series of triple action Pt(iv) prodrugs was designed to test the hypothesis that multi-action compounds, where each bioactive moiety intervenes in several cellular processes, might be more effective than a single agent at killing cancer cells. In particular, "triple action" Pt(iv) derivatives of cisplatin, where the axial ligands are inhibitors of cyclooxygenase (COXi), histone deacetylase (HDACi) or pyruvate dehydrogenase kinase (PDKi) were developed. All compounds, ctc-[Pt(NH3)2(COXi)(PDKi)Cl2], ctc-[Pt(NH3)2(COXi)(HDACi)Cl2] and ctc-[Pt(NH3)2(HDACi)(PDKi)Cl2], where COXi = aspirin or ibuprofen, PDKi = dichloroacetate and HDACi = valproate or phenylbutyrate, were significantly more cytotoxic than cisplatin against all cell lines of an in-house panel of human cancer cells. They were particularly effective against thyroid and pancreatic cancer cells in monolayer cytotoxicity tests. Remarkably, in 3D spheroid cancer cell cultures, some triple action compounds showed an antitumor potency up to 50-fold higher than cisplatin against a KRAS mutated pancreatic cancer cell line (PSN-1 cells). Standard biochemical assays classically employed to explore structure activity relationships of platinum drugs, such as cellular uptake and binding to potential biological targets (DNA, HDAC, mitochondria, and COX), do not provide linear correlations with the overall cytotoxicity data. We observed a preferential induction of ROS production and of an anti-mitochondrial effect in cancer cells compared to rapidly dividing non-cancerous cells. Thus, we propose that these new triple action Pt(iv) derivatives of cisplatin are a novel and interesting class of potent and selective cytotoxic agents.

Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)].

This report describes the synthesis, characterization and biological activity of a series of platinum(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] (Pt56MeSS) with non-bioactive, lipophilic and bioactive axial ligands. In an attempt to explore the anticancer activity potential of the Pt(iv) derivatives, 2D and 3D cytotoxic screening and a preliminary in vivo study were performed. The average IC50 values of the platinum(iv) derivatives ranged from 1.26 to 5.39 µM, compared with 1.24 µM for Pt56MeSS, suggesting that the axial ligands have a relatively minor effect on the potency of the compounds. Preliminary in vivo studies indicate that the platinum(iv) derivatives of Pt56MeSS are active in vivo and can reduce the tumor to a similar extent to cisplatin.

Probing the Interactions of Cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and Its PtIV Derivatives with Human Serum.

The discrepancy between the in vitro cytotoxic results and the in vivo performance of Pt56MeSS prompted us to look into its interactions and those of its PtIV derivatives with human serum (HS), human serum albumin (HSA), lipoproteins, and serum-supplemented cell culture media. The PtII complex, Pt56MeSS, binds noncovalently and reversibly to slow-tumbling proteins in HS and in cell culture media and interacts through the phenanthroline group with HSA, with a Kd value of ∼1.5×10-6 m. All PtIV complexes were found to be stable toward reduction in HS, but those with axial carboxylate ligands, cct-[Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenantroline)(acetato)2 ](TFA)2 (Pt56MeSS(OAc)2 ) and cct-[Pt(1S,2S-DACH)(5,6-dimehtyl-1,10-phenantroline)(phenylbutyrato)2 ](TFA)2 (Pt56MeSS(PhB)2 ), were spontaneously reduced at pH 7 or higher in phosphate buffer, but not in Tris buffer (pH 8). HS also decreased the rate of reduction by ascorbate of the PtIV complexes relative to the reduction rates in phosphate buffer, suggesting that for this compound class, phosphate buffer is not a good model for HS.

Coffee polyphenols protect human plasma from postprandial carbonyl modifications.

The antioxidant capability of coffee polyphenols to inhibit red-meat lipid peroxidation in stomach medium and absorption into blood of malondialdehyde (MDA) in humans was studied. Roasted-ground coffee polyphenols that were found to inhibit lipid peroxidation in stomach medium are 2- to 5-fold more efficient antioxidant than those found in instant coffee. Human plasma from ten volunteers analyzed after a meal of red-meat cutlets (250 g) revealed a rapid accumulation of MDA. The accumulation of MDA in human plasma modified low-density lipoprotein is known to trigger atherogenesis. Consumption of 200 mL roasted coffee by ten volunteers during a meal of red-meat cutlets, resulted after 2 and 4 h in the inhibition by 80 and 50%, respectively, of postprandial plasma MDA absorption. The results obtained in vitro simulated stomach model on MDA accumulation were predictive for the amount of MDA absorbed into circulating human plasma, in vivo. Timing the consumption of coffee during the meals may make it a very active functional food.