The QSAR studies have been carried out using topological parameters along with thermodynamic and structural descriptors. Acceptable MK-2206 values of internal and external validation parameters for the developed QSAR models confirm acceptability of the models. Pharmacophore mapping revealed that two hydrogen bond donor (HBD) features and a hydrophobic feature (HYD) are important parameters for PfDHFR-TS inhibitory activity. The docking studies suggest that the PfDHFR-TS inhibitors interact with Asp54, Ile14, Ile164, ser108, Ser111, Tyr170, Met55, Ala16, Thr185, Leu46, Cys15, Phe58, Ile112, Trp48, Tyr57 and Leu119 amino acid residues.
The QSAR, pharmacophore and docking studies inferred that i) branching of the substituents at R1 and R2 positions should be less (small alkyl chain substituents are favored); ii) the electronegativity of the molecules should be high but within some limit; iii) the size and volume of the molecules should be high; iv) molecules should be flexible enough; v) R configuration
at C6 position of the triazine ring favors the inhibitory binding affinity; vi) the substituents of the phenyl ring at 3, 4 and 5 position of the phenyl ring should be small hydrophobic groups. Based on these studies, we have designed a library of cycloguanil derivatives with good in silico Screening Library manufacturer predicted PfDHFR-TS inhibitory activity.”
“As furfural (F) and 5-hydroxymethylfurfural (HMF) are essentially formed from sugar dehydration, especially in food submitted to heat, they can be found in beverages, as well as fortified sweet wines. In order to assess the impact of temperature on Madeira winemaking, three traditional varieties of Madeira wines (Malvasia. Sercial and Tinta Negro Mole) were studied to evaluate the F and HMF contents. The wines were produced LY3023414 by two vinification processes, following traditional and modern methodologies, heated at standard conditions (30 degrees C and 45 degrees C, for 4 months) and compared with the same wines submitted to overheating conditions (55 degrees C, for 4 months). The RP-HPLC-DAD methodology used for the
control of F and HMF during the process showed no significant changes in the wines maintained at 30 degrees C (canteiro) and a noticeable but controlled increase in the wines heated at 45 degrees C (estufagem) where values up to about 150 mg/L of HMF could be found in sweet wines. The strong relation of this compound with the sugar content and baking temperature stood out in the wines submitted to overheating conditions where values higher than 1 g/L could be found for sweeter wines, with HMF level being in general higher than F.
The results clearly suggest that the amount of HMF in these fortified wines can be easily controlled when submitted to adequate conditions of heating during estufagem and storage.