Synthesis, Spectroscopic Characterization, Structural Studies, and in Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4'-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3',4'-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3',5'-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 µM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 µM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells

Actividad citotóxica del extracto etanólico de gnaphalium spicatum "keto keto" en cultivos de líneas celulares tumorales humanas

Objetivos. Evaluar la actividad citotóxica de extractos etanólicos de raíces, tallos, hojas y flores de Gnaphalium spicatum sobre algunas líneas celulares tumorales humanas. Materiales y métodos. Las líneas celulares HT-29, H-460, MCF-7, M-14, PC-3, DU-145, K-562, y 3T3, fueron expuestas a cuatro concentraciones de extractos etanólicos de raíces, tallos, hojas y flores de Gnaphalim spicatum, asimismo, a diferentes concentraciones de cisplatino, que se usó como control positivo. Se halló los porcentajes de crecimiento en 48 horas. Luego se determinó la concentración inhibitoria 50 (CI50) mediante análisis de regresión lineal, el índice de selectividad de cada muestra y finalmente, la relación dosis-respuesta entre las concentraciones de los extractos y cisplatino, con los porcentajes de crecimiento. Resultados. El extracto etanólico de las raíces de Gnaphalium spicatum mostró mayor actividad citotóxica en la líneas celulares MCF-7 y K-562. Los CI50 en μg/mL fueron de 98 (r= -0,98 p a 0,250 mg/mL en todas la líneas celulares evaluadas. Conclusiones. Los extractos etanólicos de tallos, hojas y flores de Gnaphalium spicatum no mostraron actividad citotóxica en este bioensayo. Los extractos de raíces mostraron citotoxicidad en las todas las líneas celulares tumorales, excepto en M-14. Además fueron menos citotóxicos en relación al cisplatino en la línea celular 3T3

Immune response to measles vaccine in Peruvian children

OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10³ plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-measles antigens. Measles-specific antibodies were measured by plaque reduction neutralization. FINDINGS: The humoral response developed rapidly after vaccination; only 4 of the 55 children (7%) had plaque reduction neutralization titres <200 mIU/ml 3 months after vaccination. However, only 8 out of 35 children tested (23%) had lymphoproliferative responses to measles antigens 3-4 weeks after vaccination. Children with poor lymphoproliferative responses to measles antigens had readily detectable lymphoproliferative responses to other antigens. Flow cytometric analysis of peripheral blood mononuclear cells revealed diffuse immune system activation at the time of vaccination in most children. The capacity to mount a lymphoproliferative response to measles antigens was associated with expression of CD45RO on CD4+ T-cells. CONCLUSION: The 55 Peruvian children had excellent antibody responses after measles vaccination, but only 23% (8 out of 35) generated detectable lymphoproliferative responses to measles antigens (compared with 55- 67% in children in the industrialized world). This difference may contribute to the less than uniform success of measles vaccination programmes in the developing world

In vitro antiproliferative activity of palladium(ii) thiosemicarbazone complexes and the corresponding functionalized chitosan coated magnetite nanoparticles

W. H. thanks Universidad de Lima Scientific Research institute for financial support. E. S., M. T., M.A. and J.M. thank Basal Project FB0807 (CEDENNA), and Y.E. thanks FONDECYT Project 3130418.Fondo Nacional de Desarrollo Científico y Tecnológico - Fondecy