Synthesis, molecular modeling, in vivo study, and anticancer activity of 1,2,4-triazole containing hydrazide–hydrazones derived from (S)-naproxen

PubMed ID: 31115928A new series of 1,2,4-triazole containing hydrazide–hydrazones derived from (S)-naproxen (7a–m) was synthesized in this study. The structures of these compounds were characterized by spectral (Fourier-transform infrared spectroscopy, 1H-nuclear magnetic resonance (NMR), 13C-NMR, and high-resolution electron ionization mass spectrometry) methods. Furthermore, molecular modeling of these compounds was studied on human methionine aminopeptidase-2. All synthesized compounds were screened for anticancer activity against three prostate cancer cell lines (PC3, DU-145, and LNCaP) using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium colorimetric method. Compound 7a showed the best activity against the PC3, DU-145 and LNCaP cancer cell lines with IC50 values of 26.0, 34.5, and 48.8 µM, respectively. Compounds 7b, 7k, and 7m showed anticancer activity against cancer cell lines PC3 and DU-145 with IC50 values of 43.0, 36.5, 29.3 µM and 49.8, 49.1, 31.6 µM, respectively. Compounds 7f and 7g showed anticancer activity against PC3 cells with IC50 values of 43.4 and 34.5 µM, respectively. To assess the biodistribution in mice of IRDye800, dye-labeled compound 7a or 100 µM of free dye was injected intravenously into the mice's tail. In vivo images were taken with in vivo imaging system spectrum device at 60, 120, 180, 240, 300, and 360 min after injection. At the end of 360 min, ex vivo studies were carried out to determine in which organs the dye was accumulated in the urogenital system. Ex vivo studies showed that the accumulation of compound 7a in the prostate is greater than that of the free dye, and it is concluded that compound 7a may be promising for the treatment of prostate cancer. © 2019 Deutsche Pharmazeutische GesellschaftTürkiye Bilimsel ve Teknolojik Araştirma Kurumu: 215S009, 117S435 215S009, 117S435Türkiye Bilimsel ve Teknolojik Arastirma Kurumu, Grant/Award Numbers: 215S009, 117S435; The Scientific and Technical Research Council of Turkey -- This study was supported by The Scientific and Technical Research Council of Turkey (TÜBİTAK), Research Fund Project Number: 215S009 (for synthesis, modeling, and anticancer activity)-117S435 (for in vivo procedure). The authors are grateful to Jürgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help in obtaining HR-EI and DART-MS mass spectra of the synthesized compounds. -

Development and Optimization of Self-emulsifying Drug Delivery Systems (SEDDS) for Enhanced Dissolution and Permeability of Rosuvastatin

11th International Symposium on Pharmaceutical Sciences (ISOPS) -- JUN 09-12, 2015 -- Ankara Univ, Fac Pharm, Ankara, TURKEYWOS: 000384799700008PubMed ID: 27230902Rosuvastatin calcium is commonly used statin for treatment of dyslipidemia. It has low bioavailability. The aim of this study was to develop new rosuvastatin calcium self-emulsifying drug delivery systems (SEDDS) as an alternative formulation and to evaluate the permeability of rosuvastatin calcium SEDDS by using Caco-2 cells. Rosuvastatin calcium SEDDSs were developed by using pseudo ternary phase diagram and characterized by using heating cooling cycle, robustness to dilution, stability and in vitro drug release and permeability. The permeability studies of rosuvastatin calcium SEDDS (P-app (A -> B) for F1-RS = 1.492x10(-5)+/- 0.413x10(-5) and Papp (A. B) for F2-RS= 1.254x10(-5)+/- 0.19x10(-5)) across Caco-2 cells showed that permeability value from apical to basolateral was higher than permeability value of commercial formulation (Papp (A -> B) = 7.13x10(-5)+/- 0.668x10(-5)). In conclusion, SEDDS as a drug carrier may be used as an effective and alternative hyperlipidemia therapy for oral delivery of rosuvastatin calcium