A critically chromatic graph

AbstractDirac (1960) concludes the paper by stating that he does not know whether there exists a critically 4-chromatic graph with connectivity at least 4. Here, we show the existence of such a graph

DESIGN, SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF QUINAZOLINAMINE DERIVATIVES AS BCRP AND P-GP INHIBITORS WITH IMPROVED METABOLIC STABILITY

A series of twenty-two quinazolinamine derivatives showing potent inhibitory activities on BCRP and P-gp was synthesized. The reversal study showed that when combined with the potent dual BCRP and P-gp inhibitors 7-8, 29-31, and 34, the IC50 value of mitoxantrone was decreased from 6.50 µM to the range of 0.24 - 0.35 µM for BCRP, and IC50 value of colchicine was decreased from 7.34 μM to the range of 0.12 - 0.29 µM for P-gp. Cyclopropyl quinazolinamine 29 (VKCY-1), which was a dual BCRP and P-gp inhibitor, and azide quinazolinamine 40 (VKCY-2), which was a BCRP inhibitor, were selected for mechanistic studies. The results revealed that target compound 29 (VKCY-1) changed the localization of BCRP in H460/MX20 cells and P-gp in KB-C2 cells rather than altering the expression level of BCRP or P-gp proteins, thus inhibiting the efflux of the anticancer drugs, which is different from the mechanisms of other reported ABC transporter inhibitors. Azide quinazolinamine 40 (VKCY-2), on the other hand, did not change the expression level or the localization of BCRP protein. In addition, compounds 29 (VKCY-1) and 40 (VKCY-2) significantly stimulated the ATP hydrolysis of BCRP transporter indicating that they can be competitive substrates of BCRP transporter, and thereby significantly increasing the accumulation of mitoxantrone in BCRP-overexpressing H460/MX20 cells. Azide quinazolinamine 40 (VKCY-2) with photoaffinity label can be a valuable probe for investigating the interactions of quinazolinamine derivatives with BCRP. After activation by the UV light, azide quinazolinamine 40 (VKCY-2) showed greater inhibitory effect on BCRP. Overall, this study indicated that quinazolinamine analogues can significantly reverse both BCRP- and P-gp-mediated MDR by blocking the efflux of anticancer drugs. Target compounds have the potential to be useful as BCRP and P-gp modulators to overcome MDR. The target quinazolinamine derivatives 7-8, 29-32, and 34 exhibited potency similar to that of the known BCRP inhibitor, Ko143. In addition, the P-gp inhibitory activities of quinazolinamine derivatives 7-8, 29-31, and 34 were greater than that of verapamil. Notably, the selected dual BCRP and P-gp inhibitors 7-8, 29-31, 34, and 40 showed improved metabolic stability than the standard pharmacologic tool Ko143

Kinetics and Mechanisms of Phosphorus Adsorption in Soils from Diverse Ecological Zones in the Source Area of a Drinking-Water Reservoir.

On-site soils are increasingly used in the treatment and restoration of ecosystems to harmonize with the local landscape and minimize costs. Eight natural soils from diverse ecological zones in the source area of a drinking-water reservoir in central China are used as adsorbents for the uptake of phosphorus from aqueous solutions. The X-ray fluorescence (XRF) spectrometric and BET (Brunauer-Emmett-Teller) tests and the Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) spectral analyses are carried out to investigate the soils' chemical properties and their potential changes with adsorbed phosphorous from aqueous solutions. The intra-particle diffusion, pseudo-first-order, and pseudo-second-order kinetic models describe the adsorption kinetic processes. Our results indicate that the adsorption processes of phosphorus in soils occurred in three stages and that the rate-controlling steps are not solely dependent on intra-particle diffusion. A quantitative comparison of two kinetics models based on their linear and non-linear representations, and using the chi-square (χ2) test and the coefficient of determination (r2), indicates that the adsorptive properties of the soils are best described by the non-linear pseudo-second-order kinetic model. The adsorption characteristics of aqueous phosphorous are determined along with the essential kinetic parameters

4′-[4-(Pyridin-2-yl)phen­yl]-2,2′:6′,2′′-terpyridine

In the title compound, C26H18N4, each ring is almost planar with maximum deviation of 0.012 (5) Å. In the crystal, mol­ecules are stacked by weak C—H⋯π inter­actions, forming a three-dimensional framework