Synthesis, and prediction of molecular properties and antimicrobial activity of some acylhydrazones derived from N-(arylsulfonyl)methionine

Sellitepe, Hasan Erdinc/0000-0001-5339-6940; Pannecouque, Christophe/0000-0002-1254-4473; Tatar, Esra/0000-0003-3490-8597; Kucukguzel, Ilkay/0000-0002-7188-1859; senkardes, sevil/0000-0002-0523-459X; BOZDEVECI, ARIF/0000-0002-0729-9143WOS: 000376305300013A series of 38 new acylhydrazones [3-40], derived from (2S)-4-(methylsulfanyl)-2-[[(4-methylphenyl)sulfonyl] amino]butanoic acid hydrazide [2], were synthesized and evaluated for their anti-HIV and antimicrobial activity with the further aim to develop acylhydrazones carrying an amino acid side chain. All tested compounds possess stronger activity against gram (+) bacteria. Compound 23 was found active against methicillin-resistant Staphylococcus aureus (MRSA) with a MIC value of 3.9 mu g/mL. the MIC value of compound 30 against Enterococcus faecalis, Listeria monocytogenes, and Bacillus cereus was 8 mu g/mL. A computational study for prediction of ADME and drug-like properties (solubility, drug-likeness, and drug score) as well as potential toxicity profiles of compounds 2-40 was performed using the Molinspiration online property calculation toolkit and Osiris Property Explorer. As most of our compounds meet Lipinski's rule of five, they promise good solubility and permeability. According to Osiris calculations, the majority of our compounds are supposed to be nonmutagenic and nonirritating.Research Fund of Marmara UniversityMarmara University [SAG-A-060510-0109]This work was supported by the Research Fund of Marmara University, project number: SAG-A-060510-0109

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. -