Synthesis, Characterization, and In Vitro Cytotoxic Activities of Benzaldehyde Thiosemicarbazone Derivatives and Their Palladium (II) and Platinum (II) Complexes against Various Human Tumor Cell Lines

The palladium (II) bis-chelate Pd (L1−3)2 and platinum (II) tetranuclear Pt4(L4)4 complexes of benzaldehyde thiosemicarbazone derivatives have been synthesized, and characterized by elemental analysis and IR, FAB(+)-mass and NMR (1H, 13C) spectroscopy. The complex Pd(L2)2 [HL2 = m-CN-benzaldehyde thiosemicarbazone] shows a square-planar geometry with two deprotonated ligands (L) coordinated to PdII through the nitrogen and sulphur atoms in a transarrangement, while the complex Pt4(L4)4 [HL4 = 4-phenyl-1-benzaldehyde thiosemicarbazone] has a tetranuclear geometry with four tridentate ligands coordinated to four PtII ions through the carbon (aromatic ring), nitrogen, and sulphur atoms where the ligands are deprotonated at the NH group. The in vitro antitumor activity of the ligands and their complexes was determined against different human tumor cell lines, which revealed that the palladium (II) and platinum (II) complexes are more cytotoxic than their ligands with IC50 values at the range of 0.07–3.67 μM. The tetranuclear complex Pt4(L4)4, with the phenyl group in the terminal amine of the ligand, showed higher antiproliferative activity (CI50 = 0.07–0.12 μM) than the other tested palladium (II) complexes

Novel Thiosemicarbazone Derivatives from Furan-2-Carbaldehyde: Synthesis, Characterization, Crystal Structures, and Antibacterial, Antifungal, Antioxidant, and Antitumor Activities

Ten new thiosemicarbazone derivatives, furan-2-carbaldehyde thiosemicarbazone (1), 3-methyl-furan-2-carbaldehyde thiosemicarbazone (2), 5-hydroxymethyl-furan-2-carbaldehyde thiosemicarbazone (3), 5-trifluoromethyl-furan-2-carbaldehyde thiosemicarbazone (4), 5-nitro-furan-2-carbaldehyde thiosemicarbazone (5), 5-phenyl-furan-2-carbaldehyde thiosemicarbazone (6), 5-(2-fluorophenyl)-furan-2-carbaldehyde thiosemicarbazone (7), 5-(4-methoxyphenyl)-furan-2-carbaldehyde thiosemicarbazone (8), 5-(1-naphthyl)-furan-2-carbaldehyde thiosemicarbazone (9), and 5-(1H-Pyrazol-5-yl)-furan-2-carbaldehyde thiosemicarbazone (10) were synthesized by condensing thiosemicarbazide with the respective furan-2-carbaldehyde in methanol. The prepared compounds were characterized by spectroscopic studies (FT-IR and NMR) and electrospray mass spectrometry. The molecular structures of 2, 6, 7, and 8 have also been determined by X-ray crystallography. Compounds 2, 6, and 7 crystallize in the E conformation about the N1-C6, N1-C11, and N1-C11 bonds, respectively, while 8 adopts the Z conformation about the N1-C12 bond with the presence of an intramolecular N2-H.O2 hydrogen bond. All prepared thiosemicarbazone derivatives were evaluated for their in vitro antibacterial, antifungal, and antitumor activities against Staphylococcus aureus strains, Candida albicans/Candida tropicalis fungi, and seven human tumor cell lines (HuTu80, H460, DU145, M-14, HT-29, MCF-7, and LNCaP), respectively. The antioxidant activity was also studied by the DPPH assay. Compound 5 exhibited significant antibacterial activity against Staphylococcus aureus ATCC700699 (MIC = 1 µg/mL) compared to the nitrofurantoin and gentamicin reference drugs (MIC = 1-25 and 10->100 µg/mL, respectively). Compound 4 was ten times less active than amphotericin B (MIC = 5 µg/mL) against Candida albicans (ATCC90028 and ATCC10231), while 1 exhibited a moderate effect of scavenging of DPPH radical (IC50 = 40.9 µg/mL) in comparison to ascorbic acid reference compound (IC50 = 22.0 µg/mL). Among all the studied thiosemicarbazones, 5 showed a higher cytotoxic activity (IC50 = 13.36-27.73 µ¿) in relation to the other tested compounds (IC50 = 34.84 - >372.34 µ¿) against all tested cell lines, except the LNCaP cell line, exhibiting its highest antiproliferative activity (IC50 = 13.36 µ¿) on the HuTu80 cell line. Besides, 8 and 9 exhibited high antitumor activity (IC50 = 13.31 and 7.69 µ¿, respectively) against the LNCaP cells.Revisión por pare

Citotoxic effect of Physalis peruviana (capuli) in colon cancer and chronic myeloid leukemia

Objetivo: Determinar la actividad citotóxica de Physalis peruviana en las líneas colo-205 (cáncer de colon) y K562 (leucemia mieloide crónica). Diseño: Estudio experimental. Lugar: Laboratorios del Departamento de Farmacología de la Universidad Nacional Mayor de San Marcos y de la Facultad de Ciencias y Filosofía de la Universidad Peruana Cayetano Heredia. Lima, Perú. Materiales: Líneas colo-205, K562 y 3T3 (fibroblastos normales de ratón), extractos etanólicos de hojas y tallos de P. peruviana, y 5-fluorouracilo (5-FU). Intervenciones: Las líneas colo-205, K562 y 3T3 (fibroblastos normales de ratón) fueron expuestas a extractos etanólicos de hojas y tallos de P. peruviana, y 5-fluorouracilo (5-FU) como control positivo. Principales medidas de resultados: Actividad citotóxica de Physalis peruviana en las líneas colo-205 y K562. Resultados: Los CI50 en μg/mL de P. peruviana en hojas y tallos fueron, respectivamente, 1,93 (r=-0,89 p<0,01) y 0,84 (r=-0,91 p<0,01), para colo-205, 2,42 (r=-0,98 p<0,005) y 2,1 (r=-0,98, p<0,005), para K562, 2,67 (r=-0,98 p<0,005) y 4,59 (r=-0,96 p<0,005), para 3T3. Los CI50 para 5-FU fueron: 3,57 (r=-0,96 p<0,005), 15,95 (r=-0,97 p<0,025) y 0,51 (r=-0,88 p=0,01) para colo- 205, K562 y 3T3, respectivamente. Los índices de selectividad de extractos de hojas, tallos y de 5-FU fueron, respectivamente, 1,38, 5,46, 0,14 para colo-205 y 1,10, 2,18, 0,032, para K562. Conclusiones: Los extractos etanólicos de hojas y tallos de P. peruviana son más citotóxicos que el 5-FU, en las líneas colo-205 y K562. Además, son menos citotóxicos en relación al 5-FU en la línea 3T3.Objective: To determine Physalis peruviana cytotoxic activity in the colo-205 (colon cancer) and K562 (chronic mieloid leukemia) cell lines. Design: Experimental study. Setting: San Marcos Major National University Pharmacology Department and Cayetano Heredia Peruvian University Sciences and Phylosophy Faculty laboratories. Materials: The lines colo-205, K562 and 3T3 cell lines, P. peruviana ethanolic leave and stem extracts, and 5-FU. Interventions: Colo-205, K562 and 3T3 (normal mouse fibroblasts) cell lines were exposed to P. peruviana ethanolic leave and stem extracts, and 5-FU was used as positive control. Main outcome measures: Physalis peruviana cytotoxic activity in the colo-205 and K562 cell lines. Results: The leaves and stems Physalis peruviana IC50 in μg/ml in the colo-205 and K562 cell lines was respectively 1,93 (r=-0,89 p<0,01) and 0,84 (r=-0,91 p<0,01) for colo-205, 2,42 (r=-0,98 p<0,005) and 2,1 (r=-0.98, p<0.005) for K562, and 2,67 (r=-0,98 p<0,005) and 4,59 (r=- 0,96 p<0,005) for 3T3. The 5-FU IC50 was 3,57 (r=-0,96 p<0,005), 15,95 (r=-0,97 p<0,025), and 0,51 (r=-0,88 p =0,01) for colo- 205, K562 and 3T3 respectively. The leaves and stems extracts and of 5-FU selectivity index were respectively 1,38, 5,46, 0,14 for colo-205 and 1,10, 2,18, 0,032 for K562. Conclusions: The P. peruviana leaves and steams ethanolic extracts were more cytotoxic than 5-FU in the colo-205 and K562 cell lines. Furthermore the P. peruviana cytotoxic effects were less than 5- FU for 3T3 cells

Synthesis, characterization, and in vitro cytotoxic activities of benzaldehyde thiosemicarbazone derivatives and their palladium(II) and platinum(II) complexes against various human tumor cell lines

The palladium (II) bis-chelate Pd (L 1 - 3) 2 and platinum (II) tetranuclear Pt 4 (L 4) 4 complexes of benzaldehyde thiosemicarbazone derivatives have been synthesized, and characterized by elemental analysis and IR, FAB (+) -mass and NMR (1 H, 13 C) spectroscopy. The complex Pd (L 2) 2 [H L 2 = m -CN-benzaldehyde thiosemicarbazone] shows a square-planar geometry with two deprotonated ligands (L) coordinated to Pd II through the nitrogen and sulphur atoms in a transarrangement, while the complex Pt 4 (L 4) 4 [H L 4 = 4 -phenyl-1-benzaldehyde thiosemicarbazone] has a tetranuclear geometry with four tridentate ligands coordinated to four Pt II ions through the carbon (aromatic ring), nitrogen, and sulphur atoms where the ligands are deprotonated at the NH group. The in vitro antitumor activity of the ligands and their complexes was determined against different human tumor cell lines, which revealed that the palladium (II) and platinum (II) complexes are more cytotoxic than their ligands with IC 50 values at the range of 0.07-3.67 µM. The tetranuclear complex Pt 4 (L 4) 4, with the phenyl group in the terminal amine of the ligand, showed higher antiproliferative activity (CI 50 = 0.07-0.12 µM) than the other tested palladium (II) complexes

Synthesis and Characterization of New Palladium(II) Complexes with Ligands Derived from Furan-2-carbaldehyde and Benzaldehyde Thiosemicarbazone and their in vitro Cytotoxic Activities against Various Human Tumor Cell Lines

With the ligands 4-phenyl-1-(furan-2-carbaldehyde)thiosemicarbazone, HTSC1, (1), 4-phenyl-1- (5 -phenyl-furan-2-carbaldehyde)thiosemicarbazone, HTSC2 (2), o-methoxy-benzaldehydethiosemicarbazone, HTSC3 (3), and o-cyano-benzaldehydethiosemicarbazone, HTSC4 (4), the corresponding palladium(II) complexes, Pd(TSC1)2 (5), Pd(TSC2)2 (6), Pd(TSC3)2 (7), and Pd(TSC4)2 (8) were synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structure of Pd(TSC3)2 (7) was determined by single-crystal X-ray diffraction. Complex 7 shows a squareplanar geometry, where two deprotonated ligands are coordinated to the PdII center through the nitrogen and sulfur atoms in a trans arrangement. In vitro antitumor studies against different human tumor cell lines have revealed that the palladium(II) complexes 5– 8 are more cytotoxic (IC50 values in the range of 0.21 – 3.79 µM) than their corresponding ligands (1 – 4) (> 60 µM). These results indicate that the antiproliferative activity is enhanced when thiosemicarbazone ligands are coordinated to the metal. Among the studied palladium(II) complexes, 8 exhibits high antitumor activity on K562 chronic myelogenous leukemia cells with a low value of the inhibitory concentration (IC50 = 0.21 µM)

Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2'-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3'-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2'-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1'-nitro-2'-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (–9.87¿M) exhibited higher antiproliferative activity than their free ligands (–70.86 and >250¿M) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02¿M, resp.)

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

Materiales bioinorgánicos de paladio con compuestos orgánicos derivados de la tiosemicarbazona de actividad antitumoral

El presente trabajo informa acerca de la preparación, caracterización y actividad anti tu moral de nuevos compuestos orgánicos (ligantes) del tipo tiosemicarbazona, RCH=N-NHC(S)-NH2 [R=pirrol-2-carboxaldehído y tiofeno 2-carboxaldehído] y sus complejos me tálicos de paladio(II). El análisis elemental y las técnicas espectroscópicas de infrarrojo y resonancia magnética nuclear de protón y carbono revelan que los ligantes tiosemicarbazonas están desprotonados y se encuentran enlazados al centro metálico a través de dos áto mos de nitrógeno (N) y azufre (S) en una configuración trans

Materiales bioinorgánicos de paladio y cobre con compuestos orgánicos de actividad antitumoral

En el presente trabajo se informa acerca de la preparación y caracterización de los compuestos orgánicos derivados del furaldehído tiosemicarbazona y sus respectivos complejos metálicos de paladio(II) y co bre(II). El análisis elemental y las técnicas espectroscópicas confirman las fórmulas estructurales propuestas para los ligantes orgánicos y sus respectivos complejos de paladio(II) y cobre(II). La actividad biológica in vitro de los ligantes y los complejos metálicos reveló que los complejos de paladio(II), Pd(LF4)2 y Pd(LF5)2 presentan mayor actividad citotóxica in vitro (CI50= 0.28 - 1.23 μM) con respecto a los ligantes frente a diferentes líneas de células tumorales de humano

Materiales bioinorgánicos de paladio y cobre con compuestos orgánicos de actividad antitumoral

En el presente trabajo se informa acerca de la preparación y caracterización de los compuestos orgánicos derivados del furaldehído tiosemicarbazona y sus respectivos complejos metálicos de paladio(II) y co bre(II). El análisis elemental y las técnicas espectroscópicas confirman las fórmulas estructurales propuestas para los ligantes orgánicos y sus respectivos complejos de paladio(II) y cobre(II). La actividad biológica in vitro de los ligantes y los complejos metálicos reveló que los complejos de paladio(II), Pd(LF4)2 y Pd(LF5)2 presentan mayor actividad citotóxica in vitro (CI50= 0.28 - 1.23 μM) con respecto a los ligantes frente a diferentes líneas de células tumorales de humano