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1.
Chem Pharm Bull (Tokyo) ; 72(8): 762-766, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39168613

RESUMEN

The new chalcogenylation of phosphines using nBu4N‧XCN (X = S, Se) is described. The reaction in 1,2-dichloroethane at 120 °C provided the corresponding phosphine sulfides in good to high yields. The protocol could be extended to the synthesis of phosphinic acid derivatives as well as sulfurization of poly(styrene-co-4-styryldiphenylphosphine).


Asunto(s)
Calcógenos , Fosfinas , Compuestos de Amonio Cuaternario , Fosfinas/química , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/síntesis química , Calcógenos/química , Calcógenos/síntesis química , Estructura Molecular
2.
Bioorg Chem ; 144: 107149, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38278048

RESUMEN

The combination of steroid structure and selenocyano group offers high potential for the design and synthesis of new potential anti-tumor drugs. Beginning with estradiol, a series of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives with remarkable antiproliferative activity was synthesized. Additionally, a 2,4-bisselenocyanoestradiol was synthesized by directly selenocyanating estradiol diacetate. It was found that the cytotoxicity of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives was significantly increased in comparison to the corresponding monoselenocyanate precursor, whereas the cytotoxicity of the 2, 4-bisselenocyanoestradiol derivative was significantly reduced compared to the respective monosubstituted precursor. The introduction of the second selenocyano group at different locations of estradiol shows a various impact on the cytotoxicity of the compounds. Among them, compound 3e showed the best cytotoxicity, with an IC50 value of less than 5 µM against the tested tumor cells, and strong inhibitory activities against HeLa and MCF-7 cell xenograft tumors in zebrafish, suppressing tumor cell migration and neovascularization. Notably, compound 3e was more effective at inhibiting neovascularization of MCF-7 cell xenograft tumors than the positive control 2-methoxyestradiol. Furthermore, compound 3e showed excellent anti-oxidative stress effect in zebrafish. Therefore, these estrogen bisselenocyanate compounds may be promising anti-tumor agents, warranting further investigation.


Asunto(s)
Antineoplásicos , Pez Cebra , Animales , Humanos , Relación Estructura-Actividad , Células MCF-7 , Antineoplásicos/química , Estradiol/farmacología , Estrógenos , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Línea Celular Tumoral
3.
Chemistry ; 29(59): e202301934, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37544915

RESUMEN

Herein, we describe a new method for the synthesis of α-carbonyl selenocyanates by reacting triselenium dicyanide (TSD) and styrenes under blue light irradiation and O2 atmosphere. The reactions are triggered by the formation of Se-centered radical species, followed by the addition/oxidation of the styrene π-bond. α-Carbonyl selenocyanates and α-hydroxy selenocyanates were obtained in moderate to excellent yields from aryl- and alkyl-substituted alkenes, respectively. It was demonstrated that α-carbonyl selenocyanates could be used as a synthetic platform in a multicomponent reaction strategy to prepare 2-phenylimidazo[1,2-a]pyridine derivatives, which were evaluated for their photophysical properties. Overall, this new method provides a useful tool for synthesizing α-carbonyl selenocyanates, and demonstrates their potential for use in the synthesis of other compounds, thus giving new synthetic opportunities to construct organic selenocyanate compounds.

4.
Bioorg Chem ; 138: 106624, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37295238

RESUMEN

Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.


Asunto(s)
Antiprotozoarios , Leishmaniasis , Compuestos de Selenio , Animales , Ratones , Antiprotozoarios/química , Macrófagos , Leishmaniasis/tratamiento farmacológico , Compuestos de Selenio/farmacología , Ratones Endogámicos BALB C
5.
Acta Crystallogr E Crystallogr Commun ; 79(Pt 5): 482-487, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37151823

RESUMEN

The reaction of MnCl2·2H2O with KSeCN and pyridine in water leads to the formation of the title complex, [Mn(NCSe)2(C5H5N)4], which is isotypic to its Fe, Co, Ni, Zn and Cd analogues. In its crystal structure, discrete complexes are observed that are located on centres of inversion. The Mn cations are octa-hedrally coordinated by four pyridine coligands and two seleno-cyanate anions that coordinate via the N atom to the metal centres to generate trans-MnN(s)2N(p)4 octa-hedra (s = seleno-cyanate and p = pyridine). In the extended structure, weak C-H⋯Se contacts are observed. Powder X-ray diffraction (PXRD) investigations prove that a pure sample was obtained and in the IR and Raman spectra, the C-N stretching vibrations are observed at 2058 and 2060 cm-1, respectively, in agreement with the terminal coordination of the seleno-cyanate anions. Thermogravimetric investigations reveal that the pyridine coligands are removed in two separate steps. In the first mass loss, a compound with the composition Mn(NCSe)2(C5H5N)2 is formed, whereas in the second mass loss, the remaining pyridine ligands are removed, which is superimposed with the decomposition of Mn(NCSe)2 formed after ligand removal. In the inter-mediate compound Mn(NCSe)2(C5H5N)2, the CN stretching vibration is observed at 2090 cm-1 in the Raman and at 2099 cm-1 in the IR spectra, indicating that the Mn cations are linked by µ-1,3-bridging anionic ligands. PXRD measurements show that a compound has formed that is of poor crystallinity. A comparison of the powder pattern with that calculated for the previously reported Cd(NCSe)2(C5H5N)2 indicates that these compounds are isotypic, which was proven by a Pawley fit.

6.
Molecules ; 28(7)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37049818

RESUMEN

Organothiocyanates and selenocyanates are valuable compounds, both in terms of functional group interconversion and due to their biological activities. In this contribution, we report the synthesis of a series of these important substances in a mixture of water and dimethyl carbonate (20/1 proportion) using potassium thio- or selenocyanates salts and organic bromides. The key to the effectiveness of the reaction is a chalcogen bond interaction between a selenonium salt catalyst and the organic substrate.

7.
Molecules ; 28(7)2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37050013

RESUMEN

Diiron µ-aminocarbyne complexes [Fe2Cp2(NCMe)(CO)(µ-CO){µ-CN(Me)(R)}]CF3SO3 (R = Xyl, [1aNCMe]CF3SO3; R = Me, [1bNCMe]CF3SO3; R = Cy, [1cNCMe]CF3SO3; R = CH2Ph, [1dNCMe]CF3SO3), freshly prepared from tricarbonyl precursors [1a-d]CF3SO3, reacted with NaOCN (in acetone) and NBu4SCN (in dichloromethane) to give [Fe2Cp2(kN-NCO)(CO)(µ-CO){µ-CN(Me)(R)}] (R = Xyl, 2a; Me, 2b; Cy, 2c) and [Fe2Cp2(kN-NCS)(CO)(µ-CO){µ-CN(Me)(CH2Ph)}], 3 in 67-81% yields via substitution of the acetonitrile ligand. The reaction of [1aNCMe-1cNCMe]CF3SO3 with KSeCN in THF at reflux temperature led to the cyanide complexes [Fe2Cp2(CN)(CO)(µ-CO){µ-CNMe(R)}], 6a-c (45-67%). When the reaction of [1aNCMe]CF3SO3 with KSeCN was performed in acetone at room temperature, subsequent careful chromatography allowed the separation of moderate amounts of [Fe2Cp2(kSe-SeCN)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 4a, and [Fe2Cp2(kN-NCSe)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 5a. All products were fully characterized by elemental analysis, IR, and multinuclear NMR spectroscopy; moreover, the molecular structure of trans-6b was ascertained by single crystal X-ray diffraction. DFT calculations were carried out to shed light on the coordination mode and stability of the {NCSe-} fragment.

8.
Acta Crystallogr E Crystallogr Commun ; 79(Pt 3): 216-220, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36909984

RESUMEN

Reaction of CoCl2·6H2O with KNCSe and 4-meth-oxy-pyridine in water led to the formation of the title compound, [Co(NCSe)2(C6H7NO)4] or Co(NCSe)2(4-meth-oxy-pyridine)2, which was characterized by single-crystal X-ray diffraction. Its asymmetric unit consists of one crystallographically independent Co cation, two seleno-cyanate anions and four 4-meth-oxy-pyridine coligands in general positions. In the crystal structure, the cobalt cations are sixfold coordinated by two terminal N-bonded seleno-cyanate anions and four 4-meth-oxy-pyridine coligands within a slightly distorted octa-hedral coordination. Between the complexes, weak C-H⋯Se inter-actions are found. IR spectroscopic investigations revealed that the CN stretching vibration of the anionic ligands is observed at 2068 cm-1, which is in agreement with the presence of only terminally coordinated seleno-cyanate anions. PXRD measurements prove that a pure compound was obtained. Differential thermoanalysis coupled to thermogravimetry (DTA-TG) at different heating rates shows that the TG curves are poorly resolved. PXRD measurements of the residue obtained by a TG measurement prove that an amorphous compound was obtained.

9.
Steroids ; 194: 109217, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36893827

RESUMEN

The introduction of selenium-containing functional groups into steroids to study the biological activities of related derivatives is rarely reported in the literature. In the present study, using cholesterol as raw material, four cholesterol-3-selenocyanoates and eight B-norcholesterol selenocyanate derivatives were synthesized, respectively. The structures of the compounds were characterized by NMR and MS. The results of the in vitro antiproliferative activity test showed that the cholesterol-3-selenocyanoate derivatives did not exhibit obvious inhibitory on the tested tumor cell lines. However, the B-norcholesterol selenocyanate derivatives obtained by structural modification of cholesterol showed good inhibitory activity against the proliferation of tumor cell. Among them, compounds 9b-c, 9f and 12 showed similar inhibitory activity against tested tumor cells as positive control 2-methoxyestradiol, and better than Abiraterone. At the same time, these B-norcholesterol selenocyanate derivatives displayed a strong selective inhibitory against Sk-Ov-3 cell line. Except for compound 9g, the IC50 value of all B-norcholesterol selenocyanate compounds against Sk-Ov-3 cells was less than 10 µM, and compound 9d was 3.4 µM. In addition, Annexin V-FITC/PI double staining was used to analyze the cell death mechanism. The results showed that compound 9c could induce Sk-Ov-3 cells to enter programmed apoptosis in a dose-dependent manner. Furthermore, the in vivo antitumor experiments of compound 9f against zebrafish xenograft tumor showed that 9f displayed obvious inhibitory effect on the growth of human cervical cancer (HeLa) xenograft tumor in zebrafish. Our results provide new thinking for the study of such compounds as new antitumor drugs.


Asunto(s)
Antineoplásicos , Colesterol , Animales , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Colesterol/química , Colesterol/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad , Pez Cebra/metabolismo , Cianatos/química , Cianatos/farmacología , Compuestos de Selenio/química , Compuestos de Selenio/farmacología
10.
Bioorg Chem ; 133: 106410, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36822000

RESUMEN

Most of the currently available cytotoxic agents for tackling cancer are devoid of selectivity, thus causing severe side-effects. This situation stimulated us to develop new antiproliferative agents with enhanced affinity towards tumour cells. We focused our attention on novel chalcogen-containing compounds (thiosemicarbazones, disulfides, selenoureas, thio- and selenocyanates), and particularly on selenium derivatives, as it has been documented that this kind of compounds might act as prodrugs releasing selenium-based reactive species on tumour cells. Particularly interesting in terms of potency and selectivity was a pharmacophore comprised by a selenocyanato-alkyl fragment connected to a p-phenylenediamine residue, where the nature of the second amino moiety (free, Boc-protected, enamine-protected) provided a wide variety of antiproliferative activities, ranging from the low micromolar to the nanomolar values. The optimized structure was in turn conjugated through a peptide linkage with biotin (vitamin B7), a cellular growth promoter, whose receptor is overexpressed in numerous cancer cells; the purpose was to develop a selective vector towards malignant cells. Such biotinylated derivative behaved as a very strong antiproliferative agent, achieving GI50 values in the low nM range for most of the tested cancer cells; moreover, it was featured with an outstanding selectivity, with GI50 > 100 µM against human fibroblasts. Mechanistic studies on the mode of inhibition of the biotinylated selenocyanate revealed (Annexin-V assay) a remarkable increase in the number of apoptotic cells compared to the control experiment; moreover, depolarization of the mitochondrial membrane was detected by flow cytometry analysis, and with fluorescent microscopy, what supports the apoptotic cell death. Prior to the apoptotic events, cytostatic effects were observed against SW1573 cells using label-free cell-living imaging; therefore, tumour cell division was prevented. Multidrug resistant cell lines exhibited a reduced sensitivity towards the biotinylated selenocyanate, probably due to its P-gp-mediated efflux. Remarkably, antiproliferative levels could be restored by co-administration with tariquidar, a P-gp inhibitor; this approach can, therefore, overcome multidrug resistance mediated by the P-gp efflux system.


Asunto(s)
Antineoplásicos , Citostáticos , Selenio , Humanos , Citostáticos/farmacología , Línea Celular Tumoral , Selenio/farmacología , Cianatos/farmacología , Apoptosis , Proliferación Celular , Antineoplásicos/farmacología , Antineoplásicos/química , Relación Estructura-Actividad
11.
Antioxidants (Basel) ; 12(2)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36830036

RESUMEN

Extracellular traps are released by neutrophils and other immune cells as part of the innate immune response to combat pathogens. Neutrophil extracellular traps (NETs) consist of a mesh of DNA and histone proteins decorated with various anti-microbial granule proteins, such as elastase and myeloperoxidase (MPO). In addition to their role in innate immunity, NETs are also strongly linked with numerous pathological conditions, including atherosclerosis, sepsis and COVID-19. This has led to significant interest in developing strategies to inhibit NET release. In this study, we have examined the efficacy of different antioxidant approaches to selectively modulate the inflammatory release of NETs. PLB-985 neutrophil-like cells were shown to release NETs on exposure to phorbol myristate acetate (PMA), hypochlorous acid or nigericin, a bacterial peptide derived from Streptomyces hygroscopicus. Studies with the probe R19-S indicated that treatment of the PLB-985 cells with PMA, but not nigericin, resulted in the production of HOCl. Therefore, studies were extended to examine the efficacy of a range of antioxidant compounds that modulate HOCl production by MPO to prevent NETosis. It was shown that thiocyanate, selenocyanate and various nitroxides could prevent NETosis in PLB-985 neutrophils exposed to PMA and HOCl, but not nigericin. These results were confirmed in analogous experiments with freshly isolated primary human neutrophils. Taken together, these data provide new information regarding the utility of supplementation with MPO inhibitors and/or HOCl scavengers to prevent NET release, which could be important to more specifically target pathological NETosis in vivo.

12.
Acta Crystallogr E Crystallogr Commun ; 79(Pt 2): 90-94, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36793409

RESUMEN

The reaction of nickel chloride hexa-hydrate with potassium seleno-cyanate and pyridine in water leads to the formation of crystals of the title complex, [Ni(NCSe)2(C5H5N)4], which were characterized by single-crystal X-ray diffraction. Its crystal structure consists of discrete complexes, located on centers of inversion, in which the Ni cations are sixfold coordinated by two terminal N-bonded seleno-cyanate anions and four pyridine ligands within a slightly distorted octa-hedral coordination. In the crystal, the complexes are connected by weak C-H⋯Se inter-actions. PXRD investigations revealed that a pure crystalline phase has formed. In the IR and Raman spectra, the C-N stretching vibrations are observed at 2083 and 2079 cm-1, respectively, in agreement with the presence of only terminally bonded anionic ligands. Upon heating, one well-resolved mass loss is observed, in which two of the four pyridine ligands are removed, leading to a compound with the composition Ni(NCSe)2(C5H5N)2. In this compound, the C-N stretching vibration is shifted to 2108 cm-1 (Raman) and 2115 cm-1 (IR), indicating the presence of µ-1,3-bridging anionic ligands. In its PXRD pattern, very broad reflections are observed, indicating for poor crystallinity and/or very small particle size. This crystalline phase is not isotypic to its Co and Fe analogs.

13.
Nanomaterials (Basel) ; 12(12)2022 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-35745375

RESUMEN

Selenium as a nutrient has a narrow margin between safe and toxic limits. Hence, wastewater discharges from selenium-containing sources require appropriate treatment that considers health concerns and stringent selenium-related water treatment standards. This work examined the use of a photocatalysis-cum-adsorption system based on a layered double hydroxide coupled with TiO2 (LDH-TiO2) to remove aqueous phase selenocyanate (SeCN−), which is difficult to treat and requires specific treatment procedures. The synthesized LDH and LDH-TiO2 composite samples were characterized using the X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetry analysis (TGA) methods. The XRD results for the uncalcined LDH indicated a hydrotalcite mass with a rhombohedral structure, whereas increasing the calcination temperature indicated transition to an amorphous state. FESEM results for the LDH-TiO2 matrix indicated round titanium dioxide particles and LDH hexagonal layers. The TGA findings for uncalcined LDH showed a gradual decrease in weight up to 250 °C, followed by a short plateau and then a sharp decrease in LDH weight from 320 °C, with a net weight loss around 47%. Based on the characterization and initial selenocyanate adsorption results, the 250 °C calcined LDH-TiO2 matrix was used for the selenocyanate photocatalysis. A ~100% selenium removal was observed using LDH:TiO2 at a 1.5:1 w/w ratio with a 2 g/L dose, whereas up to 80% selenium removal was noted for LDH:TiO2 at a 0.5:1 w/w ratio. The respective difference in the efficiency of selenium treatment was attributed to enhanced LDH-based adsorption sites in the enhanced LDH:TiO2 w/w ratio. Furthermore, the selenite and selenate that occurred during SeCN− photocatalytic degradation (PCD) were also nearly completely removed via adsorption. An optimization exercise using response surface methodology (RSM) for total selenium removal showed R2 values of more than 0.95, with a prediction accuracy of more than 90%. In summary, the present findings show that the use of a photocatalysis-cum-adsorption system based on LDH-TiO2 is a promising technique to treat industrial wastewater discharges for selenocyanate and also remove the resulting intermediates.

14.
Steroids ; 181: 108992, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35202703

RESUMEN

Selenocyano fragments with different structural characteristics have been successfully installed into the 3- and 17-position of estradiol through the etherification and esterification of its 3 or 17-hydroxyl group respectively. A total of 12 new estradiol selenocyanates were synthesized and their structures were characterized by NMR and HRMS. The tumor cell lines related to the expression of human hormones were selected as the screening objects, and the antiproliferative activity of the target compounds was further investigated. The results showed that the introduction of selenocyano group in estradiol could endue estradiol with the activity of inhibiting tumor cell proliferation, and 3-selenocyanoalkyl estradiol ethers had stronger cytotoxicity than their 17-selenocyanocarboxylates counterpart. Among them, IC50 value of compound 3e on HeLa cells was 5.69 µM. The information obtained from the studies may be useful for the design and development of novel chemotherapeutic drugs.


Asunto(s)
Antineoplásicos , Estradiol , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estradiol/farmacología , Células HeLa , Humanos , Estructura Molecular , Relación Estructura-Actividad
15.
Curr Org Synth ; 2021 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-34951576

RESUMEN

A convenient, efficient, and general procedure for the synthesis of diaryl diselenides has been developed by the reaction of aryl diazonium tetrafluoroborates and Potassium Selenocyanate on the surface of alumina under ball-milling in absence of any solvent, transition metal catalyst and base in room temperature. A wide range of functionalized diaryl diselenides are obtained in high purity and high yield by this procedure. BACKGROUND: Synthesis of diaryl diselenides was restricted into only few Cu-catalyzed C-Se Cross coupling protocol where use of ligands, high reaction temp, long reaction time were required. OBJECTIVE: To achieve a sustainable protocol for the synthesis of diaryl diselenides Method: Reaction of aryl diazonium fluoroborate with KSeCN was successfully performed under ball milling in absence of any ransition metal catalyst, ligands, base and external heating to get diaryl diselenides. RESULTS: A library of diaryl diselenides were obtained in good yields with different functional groups. CONCLUSION: First transition metal free protocol for the synthesis of diaryl diselenides has been developed successfully.

16.
Artículo en Inglés | MEDLINE | ID: mdl-34508979

RESUMEN

The simultaneous detection of cyanide (CN), thiocyanate (SCN), and selenocyanate (SeCN) by a HPLC-fluorescence detector (FLD) with the post-column König reaction was recently reported. SCN and SeCN are also detectable by HPLC-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) because sulfur and selenium can be detected, respectively, without any pre- or post-treatment. ICP-MS has high sensitivity for selenium and sulfur detection and is robust to sample matrices. In this study, we compared HPLC-FLD with the post-column König reaction and HPLC-ICP-MS in terms of SCN and SeCN detection sensitivity and linearity. The limit of detection (LOD) for SCN indicated that HPLC-FLD with the post-column König reaction was 354 times more sensitive than HPLC-ICP-MS. Likewise, the LOD for SeCN indicated that HPLC-FLD was 51 times more sensitive than HPLC-ICP-MS. These results demonstrated that HPLC-FLD was a more suitable technique for SeCN and SCN detection than HPLC-ICP-MS. We previously reported that SeCN was generated in selenite-exposed mammalian cells to detoxify excess selenite. HPLC-FLD with the post-column König reaction enabled good separation and detection for quantifying SCN and SeCN in mammalian cell lines exposed to selenite. The intracellular SCN and SeCN concentrations determined by this technique suggested differences in the metabolic capacity for selenite to form SeCN among the cell lines. In addition, since the amount of intracellular SCN and SeCN were significantly decreased by pretreatment of myeloperoxidase (MPO) inhibitors, SCN and SeCN were resulted from the interaction of sulfur and selenium with endogenous CN, respectively, generated with MPO.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Cianatos/análisis , Espectrometría de Masas/métodos , Compuestos de Selenio/análisis , Espectrometría de Fluorescencia/métodos , Tiocianatos/análisis , Cianatos/metabolismo , Células Hep G2 , Humanos , Límite de Detección , Modelos Lineales , Compuestos de Selenio/metabolismo , Tiocianatos/metabolismo
17.
Future Med Chem ; 13(19): 1655-1677, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34427101

RESUMEN

Hepatocellular carcinoma is a highly aggressive and difficult-to-treat type of cancer. Incorporating urea functionality into the backbone of organoselenium compounds is expected to develop promising chemotherapeutic leads against liver cancer. Methods: Urea-functionalized organoselenium compounds were synthesized in good yields, and their cytotoxicity was evaluated against HepG2 cells. Results: 1,1'-(Diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) exhibited efficient anti-HepG2 activity in sub-micromolar concentrations, with no toxicity to normal human skin fibroblasts. The molecular mechanisms of the diselenide-based urea 14 were evaluated using colony formation, wound healing, 3D spheroid invasion assays, cell cycle analysis and apoptosis induction. Its redox properties were also assessed by using different bioassays. Conclusion: Our study revealed promising anticancer, antimigratory and anti-invasiveness properties of 1,1'-(diselanediylbis(4,1-phenylene))bis(3-phenylurea) (14) against HepG2.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Urea/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Estructura Molecular , Compuestos de Organoselenio/química , Urea/química
18.
Antimicrob Agents Chemother ; 65(10): e0059021, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34339279

RESUMEN

This work reports the synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), 1H, 13C, and 79Se nuclear magnetic resonance (NMR), mass spectrometry, and elemental analysis techniques as well as the in vitro evaluation of the leishmanicidal activity of 13 new selenophosphoramidate derivatives. Among the new compounds, four of them (compounds 1f, 1g, 2f, and 2g), which exhibited the best profiles, were tested against infected macrophages and were selected for further studies related to their leishmanicidal mechanism. In this regard, trypanothione redox system alteration was determined. Compound 1g, under similar conditions, was more effective than the corresponding references. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that selenophosphoramidate functionalities may represent a scaffold to be explored toward the development of new agents for leishmania treatment.


Asunto(s)
Antiprotozoarios , Leishmania , Preparaciones Farmacéuticas , Selenio , Amidas , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Ácidos Fosfóricos , Selenio/farmacología
19.
Antioxidants (Basel) ; 10(4)2021 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-33920484

RESUMEN

Breast cancer is a multifactor disease, and many drug combination therapies are applied for its treatment. Selenium derivatives represent a promising potential anti-breast cancer treatment. This study reports the cytotoxic activity of forty-one amides and phosphoramidates containing selenium against five cancer cell lines (MCF-7, CCRF-CEM, HT-29, HTB-54 and PC-3) and two nonmalignant cell lines (184B5 and BEAS-2B). MCF-7 cells were the most sensitive and the selenoamides I.1f and I.2f and the selenium phosphoramidate II.2d, with GI50 values ranging from 0.08 to 0.93 µM, were chosen for further studies. Additionally, radical scavenging activity for all the compounds was determined using DPPH and ABTS colorimetric assays. Phosphoramidates turned out to be inactive as radical scavengers. No correlation was observed for the antioxidant activity and the cytotoxic effect, except for compounds I.1e and I.2f, which showed dual antioxidant and antitumor activity. The type of programmed cell death and cell cycle arrest were determined, and the results provided evidence that I.1f and I.2f induced cell death via autophagy, while the derivative II.2d provoked apoptosis. In addition, Western blot analysis corroborated these mechanisms with an increase in Beclin1 and LC3-IIB and reduced SQSTM1/p62 levels for I.1f and I.2f, as well as an increase in BAX, p21 and p53 accompanied by a decrease in BCL-2 levels for derivative II.2d.

20.
Redox Biol ; 41: 101873, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33550113

RESUMEN

The production of hypochlorous acid (HOCl) by myeloperoxidase (MPO) plays a key role in immune defense, but also induces host tissue damage, particularly in chronic inflammatory pathologies, including atherosclerosis. This has sparked interest in the development of therapeutic approaches that decrease HOCl formation during chronic inflammation, including the use of alternative MPO substrates. Thiocyanate (SCN-) supplementation decreases HOCl production by favouring formation of hypothiocyanous acid (HOSCN), which is more selectively toxic to bacterial cells. Selenium-containing compounds are also attractive therapeutic agents as they react rapidly with HOCl and can be catalytically recycled. In this study, we examined the ability of SCN-, selenocyanate (SeCN-) and selenomethionine (SeMet) to modulate HOCl-induced damage to human coronary artery smooth muscle cells (HCASMC), which are critical to both normal vessel function and lesion formation in atherosclerosis. Addition of SCN- prevented HOCl-induced cell death, altered the pattern and extent of intracellular thiol oxidation, and decreased perturbations to calcium homeostasis and pro-inflammatory signaling. Protection was also observed with SeCN- and SeMet, though SeMet was less effective than SeCN- and SCN-. Amelioration of damage was detected with sub-stoichiometric ratios of the added compound to HOCl. The effects of SCN- are consistent with conversion of HOCl to HOSCN. Whilst SeCN- prevented HOCl-induced damage to a similar extent to SCN-, the resulting product hyposelenocyanous acid (HOSeCN), was more toxic to HCASMC than HOSCN. These results provide support for the use of SCN- and/or selenium analogues as scavengers, to decrease HOCl-induced cellular damage and HOCl production at inflammatory sites in atherosclerosis and other pathologies.


Asunto(s)
Ácido Hipocloroso , Selenio , Humanos , Músculo Liso Vascular , Miocitos del Músculo Liso , Peroxidasa , Tiocianatos
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