1.Pharmacokinetic properties of tandem d-peptides designed for treatment of Alzheimer's disease.
Leithold LH1, Jiang N2, Post J3, Niemietz N4, Schartmann E5, Ziehm T6, Kutzsche J7, Shah NJ8, Breitkreutz J9, Langen KJ10, Willuweit A11, Willbold D12. Eur J Pharm Sci. 2016 Apr 13. pii: S0928-0987(16)30119-1. doi: 10.1016/j.ejps.2016.04.016. [Epub ahead of print]
Peptides are more and more considered for the development of drug candidates. However, they frequently exhibit severe disadvantages such as instability and unfavourable pharmacokinetic properties. Many peptides are rapidly cleared from the organism and oral bioavailabilities as well as in vivo half-lives often remain low. In contrast, some peptides consisting solely of d-enantiomeric amino acid residues were shown to combine promising therapeutic properties with high proteolytic stability and enhanced pharmacokinetic parameters. Recently, we have shown that D3 and RD2 have highly advantageous pharmacokinetic properties. Especially D3 has already proven promising properties suitable for treatment of Alzheimer's disease. Here, we analyse the pharmacokinetic profiles of D3D3 and RD2D3, which are head-to-tail tandem d-peptides built of D3 and its derivative RD2. Both D3D3 and RD2D3 show proteolytic stability in mouse plasma and organ homogenates for at least 24h and in murine and human liver microsomes for 4h.
2.Design and synthesis of some novel 4-Chloro-N-(4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)phenyl) benzenesulfonamide derivatives as anticancer and radiosensitizing agents.
Ghorab MM1, Ragab FA2, Heiba HI3, Soliman AM3. Eur J Med Chem. 2016 Apr 6;117:8-18. doi: 10.1016/j.ejmech.2016.04.009. [Epub ahead of print]
A novel series of sulfonamide derivatives 4-21 have been synthesized starting from the strategic starting material (E)-4-Chloro-N-(4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)phenyl) benzenesulfonamide 4. Two series of hydrazone 5-9, and pyridone 10-21 derivatives bearing a sulfonamide moiety were obtained. All the newly synthesized compounds were evaluated for their in vitro cytotoxic activity against human liver cancer cell line (HepG2). Compounds 4-6, 8, 9, 10-14 and 16-18 showed higher activity compared to doxorubicin as a positive control. The radiosensitizing ability of the most promising compounds 4, 10 and 12 was studied which showed an increase in the cell killing effect of γ-radiation after combination with these derivatives. The molecular design was performed to predict the binding mode of the most promising compounds 4, 10 and 12 with the active site of hCA IX, that showed appropriate fitting with the relevant amino acids in the binding pocket on the basis of standard bond lengths, angles, S score and E conformation data.
3.Local and traditional uses, phytochemistry, and pharmacology of Sophora japonica L.: A review.
He X1, Bai Y2, Zhao Z2, Wang X2, Fang J2, Huang L3, Zeng M2, Zhang Q2, Zhang Y2, Zheng X4. J Ethnopharmacol. 2016 Apr 13. pii: S0378-8741(16)30205-7. doi: 10.1016/j.jep.2016.04.014. [Epub ahead of print]
ETHNOPHARMACOLOGICAL RELEVANCE: Sophora japonica (Fabaceae), also known as Huai (Chinese: ), is a medium-sized deciduous tree commonly found in China, Japan, Korea, Vietnam, and other countries. The use of this plant has been recorded in classical medicinal treatises of ancient China, and it is currently recorded in both the Chinese Pharmacopoeia and European Pharmacopoeia. The flower buds and fruits of S. japonica, also known as Flos Sophorae Immaturus and Fructus Sophorae in China, are most commonly used in Asia (especially in China) to treat hemorrhoids, hematochezia, hematuria, hematemesis, hemorrhinia, uterine or intestinal hemorrhage, arteriosclerosis, headache, hypertension, dysentery, dizziness, and pyoderma. To discuss feasible trends for further research on S. japonica, this review highlights the botany, ethnopharmacology, phytochemistry, biological activities, and toxicology of S. japonica based on studies published in the last six decades.
4.Antioxidant capacity of different cheeses: Affecting factors and prediction by near infrared spectroscopy.
Revilla I1, González-Martín MI2, Vivar-Quintana AM3, Blanco-López MA3, Lobos-Ortega IA4, Hernández-Hierro JM5. J Dairy Sci. 2016 Apr 13. pii: S0022-0302(16)30171-0. doi: 10.3168/jds.2015-10564. [Epub ahead of print]
In this study, we analyzed antioxidant capacity of 224 cheese samples prepared using 16 varied mixtures of milk from cows, ewes, and goats, in 2 manufacturing seasons (winter and summer), and over 6 mo of ripening. Antioxidant capacity was evaluated using the spectrophotometric 2,2-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid) (ABTS) method. Total antioxidant capacity was significantly correlated with season of manufacturing and time of ripening but not with animal species providing the milk. Moreover, statistically significant correlations between the total antioxidant capacity and retinol (r = 0.399), fat percentage (r = 0.308), protein percentage (r = 0.366), K (r = 0.385), Mg (r = 0.312), Na (r = 0.432), and P (0.272) were observed. We evaluated the use of near infrared spectroscopy technology, together with the use of a remote reflectance fiber-optic probe, to predict the antioxidant capacity of cheese samples. The model generated allowed us to predict antioxidant capacity in unknown cheeses of different compositions and ripening times.
