ABSTRACT
Abstract This paper reports the synthesis and detailed characterization of six novel lanthanide complexes of La(III), Eu(III) and Nd(III) with N(4)-substituted thiosemicarbazones derived from the 2-carboxybenzaldehyde. The IR, 1H-NMR and 13C-NMR spectroscopic studies confirmed the coordination of the thiocarbonyl (C=S), azomethine (C=N) and carboxylate (COO-) groups to the metal centers, and the carboxylate was coordinated in a bidentate manner. The elemental and thermal analyses suggest that lanthanide complexes were formed in 1:2 molar ratios (metal:ligand). The molar conductivity values confirmed the non-electrolytic nature of the complexes. The interaction of these complexes with calf thymus DNA (CT-DNA) was investigated by UV absorption and viscosity measurements. It was found that the Eu(HI) and Nd(nI) complexes could roll along the DNA strands through groove interactions. Furthermore, lanthanide complexes could promote the oxidative cleavage of plasmid pBR322 in a high-oxidative stress environment. Finally, the Schiff base ligands (L) and their complexes were evaluated for their antibacterial activities against gram-positive and gram-negative bacteria using a microdilution procedure. The results indicate that the lanthanide complexes exhibit more potent antibacterial activity than the free ligands.
Resumen Este articulo reporta la síntesis y caracterización detallada de seis nuevos complejos lantánidos de La(III), Eu(III) y Nd(III) con tiosemicarbazonas N(4)-sustituidas derivadas del 2-carboxibenzaldehído. Los estudios espectroscópicos de IR, 1H-NMR y 13C-NMR confirmaron la coordinación de los grupos tiocarbonilo (C=S), azometina (C=N) y carboxilato (COO-) a los centros metálicos, y el carboxilato se coordinó de forma bidentada. Los análisis elemental y térmico sugieren que los complejos lantánidos se formaron en proporciones molares 1:2 (metal:ligando). Los valores de conductividad molar confirmaron la naturaleza no eléctrica de los complejos. Por medio de medidas de absorción UV y de viscosidad se investigó la interacción entre estos complejos con DNA de timo de ternera (CT-DNA). Se encontró que los complejos Eu(III) y Nd(III) podrían correr a lo largo de cadenas de DNA a través de interacciones en el surco. Además, los complejos lantánidos podrían promover el clivaje oxidativo del plásmido pBR322 en un ambiente de alto estrés oxidativo. Finalmente, se evaluaron las actividades antibacteriales de las bases de Schiff como ligandos (L) y sus complejos contra bacterias gram-positivas y gram-negativas usando un procedimiento de microdilución. Los resultados indican que los complejos lantánidos exhiben una actividad antibacterial más potente que los ligandos libres.
Resumo Este artigo reporta a síntese e caracterização detalhada de seis novos complexos lantanídeos de La(III), Eu(III) e Nd(III) com tiosemicarbazonas N(4)-substituídas derivadas do 2-carboxibenzaldeído. Os estudos espectroscópicos de IR, 1H-RMN e 13C-RMN confirmaram a coordenação dos grupos tiocarbonilos (C = S), azometina (C=N) e carboxilato (COO-) com os centros metálicos, e o carboxilato se coordenou de forma bidentada. As análises elementares e térmicas sugerem que os complexos lantanídeos se formaram em proporções molares 1:2 (metal:ligante). Os valores de condutividades molar confirmaram a natureza não-elétrica dos complexos. Se avaliou a interação entre estes complexos com DNA de vitela (CT-DNA) por meio de medidas de absorção UV e de viscosidade. Se observou que os complexos Eu(III) e Nd(III) poderiam deslocar-se ao longo da cadeia de DNA através de interações no sulco. Adicionalmente, os complexos lantanídeos poderiam promover a clivagem oxidativa do plasmídeo pBR322 em um ambiente de alto estresse oxidativo. Finalmente, se avaliaram as atividades antibacterianas das bases de Schiff como ligantes (L) e seus complexos contra bactérias gram-positivas e gram- negativas, usando o método de microdiluição. Os resultados indicam que os complexos lantanídeos exibem uma atividade antibacteriana mais potente que os ligantes livres.
Subject(s)
Thiosemicarbazones , DNA , Lanthanoid Series Elements/chemistry , Anti-Bacterial AgentsABSTRACT
ABSTRACT The aims of this study were to synthesize a series of thiosemicarbazones and their thiazole derivatives, to investigate their cytotoxic activity against three human cancers and normal (Vero cells) cell lines, and to evaluate the pro-apoptotic potential of the most active compounds. Materials and Methods: The thiosemicarbazones were obtained by reacting an aromatic aldehyde with thiosemicarbazide (yield 71-96%), which were subjected to a cyclization with α-bromoacetophenone to yield the required thiazole heterocycles (yield 63-100%). All the synthesized compounds were screened at 50 µM concentration against three cell lines representing HL60 (promyelocytic leukemia), Jurkat (acute lymphoblastic leukemia), and MCF-7 (breast cancer). The pro-apoptotic effect was measured by flow cytometry as the percentage of cells with hypodiploid DNA. Results: Three thiazole compounds showed activity against at least one tumor cell line (IC50 = 43-76 µM) and low cytotoxicity against Vero cells (IC50 > 100 M). The most active compound of this series induced 91% and 51% DNA fragmentation in HL60 and MCF-7 cell lines, respectively, suggesting that this compound triggered apoptosis in these cells. Conclusion: Among the synthesized compounds, one in particular was found to exert antiproliferative and pro-apoptotic activity on tumor cells and can be considered promising as a lead molecule for the design of new analogues with improved activity.
RESUMO O estudo teve como objetivo a síntese de uma série de tiossemicarbazonas e seus derivados tiazólicos e a avaliação da atividade citotóxica contra três linhagens de células tumorais humanas e células normais (Vero), a fim de se avaliar o potencial pró-apoptótico dos compostos mais ativos. As tiossemicarbazonas foram obtidas por reação entre um aldeído aromático e tiossemicarbazida (rend. 71-96%), as quais foram submetidas à ciclização com α-bromoacetofenona, fornecendo os heterociclos tiazólicos desejados (rend. 63-100%). Todos os compostos sintetizados foram testados na concentração de 50 µM contra três linhagens de células tumorais: HL60 (leucemia promielocítica), Jurkat (leucemia linfoblástica aguda) e MCF-7 (câncer de mama). O efeito pró-apoptótico foi avaliado por citometria de fluxo como porcentagem de células com DNA hipodiplóide. Três compostos tiazólicos foram ativos contra, pelo menos, uma linhagem tumoral (CI50=43-76 µM), com baixa citotoxicidade contra células Vero (CI50 > 100 M). O composto mais ativo dessa série induziu fragmentação do DNA de 91% e 51% nas linhagens HL60 e MCF-7, respectivamente, sugerindo que este composto ativou a apoptose nessas células. Dentre os compostos sintetizados, um em particular apresentou atividade antiproliferativa e pró-apoptótica em células tumorais e pode ser considerado composto protótipo promissor na busca por novos análogos com atividade melhorada.
Subject(s)
Thiazoles/chemistry , Thiosemicarbazones/toxicity , Vero Cells , Cell Line, TumorABSTRACT
Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical research. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel approach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (sodium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs. The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associated markers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcinogenicity and the use of exogenous reprogramming factors.
Subject(s)
Animals , Mice , Amides , Pharmacology , Butyric Acid , Pharmacology , Cell Differentiation , Cell Line , Cell Proliferation , Extraembryonic Membranes , Cell Biology , Folic Acid , Pharmacology , Induced Pluripotent Stem Cells , Cell Biology , Kruppel-Like Transcription Factors , Metabolism , Octamer Transcription Factor-3 , Metabolism , Proto-Oncogene Proteins c-myc , Metabolism , Pyrazoles , Pharmacology , Pyridines , Pharmacology , Pyrimidines , Pharmacology , SOXB1 Transcription Factors , Metabolism , Thiocarbamates , Pharmacology , ThiosemicarbazonesABSTRACT
Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Naphthoquinones/pharmacology , Semicarbazones/pharmacology , Thiosemicarbazones/pharmacology , Cryptococcus gattii/drug effects , Enterococcus faecalis/drug effects , Microbial Sensitivity Tests , Paracoccidioides/drug effects , Staphylococcus aureus/drug effectsABSTRACT
A new reagent, [2E, 2Z]2,2-[3[E]-[2-hydroxyphenyl] diazenyl] pentane-2,4-diylidene] bis [hydrazinecarbothioamide] [OPTS] was synthesized and studied. Acid-base, spectrophotometric properties of OPTS were studied in 50% ethanol-water mixture solutions at pH 3-11. Ionization constants of the reagent OPTS have been determined by a spectrophotometric and potentiometric titrations: pK[1]=9.60 +/- 0.02; pK[2]= 10.45 +/- 0.05 in its computational and graphical versions at an ionic strength 0.1 M Na10[4]. The stability constants of the Ag-OPTS are logK[1]=4.55 +/- 0.04 and 10gK[2]=3.92 +/- 0.05. The reaction of Ag [I] with OPTS gives a mononuclear complex in 50% ethanol water mixture solution with lambda[max]=462 nm at pH=8.1. The effects of foreign ions and masking agents on the determination of Ag [I] with the new reagent are studied. The mono complex obeys the Beer's law in the Ag [I] concentration range 1.1-17 mg/25ml. Molar absorption coefficients were determined. In this paper, we report the synthesis of the novel Ag [l] complexes with OPTS. The complexes were characterized by UV-Vis and IR spectroscopy, elemental analysis, molar conductivity and thermal decomposition
Subject(s)
Spectrum Analysis/methods , Potentiometry/methods , ThiosemicarbazonesABSTRACT
Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50 percent of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.
Subject(s)
Animals , Antiprotozoal Agents/pharmacology , Thiazoles/pharmacology , Thiosemicarbazones/pharmacology , Toxoplasma/drug effects , Antiprotozoal Agents/chemistry , Chlorocebus aethiops , Host-Parasite Interactions , Microscopy, Electron, Transmission , Parasitic Sensitivity Tests , Thiazoles/chemistry , Thiosemicarbazones/chemistry , Toxoplasma/ultrastructure , Vero Cells/parasitologyABSTRACT
Complexes from of 5-methyl-3-furaldehydethiosemicarbazone [5M3HFTSC] and Hg[II] salts derived from inorganic [HCl] and organic hallo acids [CHCl2COOH or CF3COOH] have been prepared. There chemical structures were characterized using elemental analyses, conductivity spectral measurements, thermogravimetric methods and photochemical behaviours. The thermal studies of such complexes using thermogravimetric analysis [TGA], derivatives thermogravimetry [DrTG] from ambient temperature to 750°C showed three decomposition steps. These studies indicated that the thermal decompositions are not simples. The photolysis of the studied compounds has been carried out in the presence of H2O2. It was found that, the photolysis was enhanced in the presence of H2O2 due to the generation of .OH radicals which are very strong oxidizing agent. Biological activity of theses compounds was tested and screened for their in-vitro antibacterial and antifungal activity. The mixed ligand complexes generally are more active than the binary and free thiosemicarbazne ligand
Subject(s)
Thiosemicarbazones/pharmacology , Thiosemicarbazones/chemical synthesis , Thermogravimetry/methods , Photolysis/drug effectsABSTRACT
Os tratamentos disponíveis para a Doença de Chagas e as leishmanioses não são eficientes e apresentam alta toxicidade. Efeito sinérgico tem sido demonstrado, quando drogas referência e novos compostos, são associados e utilizados contra estas patologias. Tiossemicarbazonas (TS) e semicarbazonas (SC) são classes de compostos com importante atividade sobre vários patógenos, incluindo o T. cruzi e a Leishmania sp. Na presente tese foram avaliados in vitro, os efeitos de três derivados de tiossemicarbazonas [estiril-tiosemicarbazona, (2-metoxi-estiril)-tiosemicarbazona e (3-metoxi-4-hidroxi-estiril)-tiosemicarbazona] e de duas semicarbazonas [(2-metoxi-estiril)-semicarbazona e (3-metoxi-4-hidroxi-estiril)-semicarbazona] sobre o T. cruzi e a Leishmania (L.) amazonensis. Nossos resultados revelaram a excelente atividade antiparasitária da maioria dos compostos, sendo que as tiossemicarbazonas mostraram-se mais ativas sobre formas tripomastigotas de T. cruzi em relação as formas promastigotas de L. (L.) amazonensis. Também observamos que a (2-metoxi-esteril)-tiossemicarbazona foi mais efetiva sobre formas amastigotas de T. cruzi, presentes em culturas de macrófagos humanos, em comparação aos parasitos intracelulares alojados em macrófagos peritoneais de camundongos, infectados in vitro. Os ensaios de associação dos compostos as drogas de referência Benzonidazol (BZ) para T. cruzi e Pentamidina (PT) para L. (L) amazonensis), revelaram uma importante potencialização da ação tripanocida e leishmanicida das TS e SC, apresentando baixa toxicidade sobre células de mamíferos. Nossos resultados promissores reforçam a importância da continuidade destes estudos, de modo a identificar terapias mais eficientes para o tratamento das doenças de Chagas e leishmanioses.
Subject(s)
Mice , Chagas Disease/epidemiology , In Vitro Techniques , Leishmania , Leishmaniasis/epidemiology , Semicarbazones , Thiosemicarbazones , Trypanosoma cruziABSTRACT
[64]Cu-pyruvaldehyde-bis [N[4]-methylthiosemicarbazone] [64]Cu-PTSM] is one of the most important copper radiopharmaceuticals used in clinical experiments. In this work, copper-64 [T[1/2]=12.33 h] production has been presented followed by the synthesis of the complexing agent, PTSM, and its structure was confirmed by common spectroscopic methods followed by radiolabeling with [64] Cu-actetate. The tracer was finally administered to fibrosarcoma-bearing rats and the biodistribution was determined in critical tissues as well as tumor. The final radiopharmaceutical solution underwent common quality control tests for animal injection a radiochemical purity >95% was determined. A significant tracer tumor uptake was observed 2 hours post injection. Tumonmuscle and tumonblood ratios were shown to be 8 and 6 respectively. [64]Cu-PTSM prepared in this report is a good candidate for tumor therapy as well as diagnosis for national use
Subject(s)
Animals, Laboratory , Radiopharmaceuticals , Organometallic Compounds , Copper Radioisotopes , Rats , ThiosemicarbazonesABSTRACT
3-aryl- 1,4,5-trihydro-1,2,4-triazole-5-thiones [2], 2-substitutcd- 1,2,3- trihydro- 1,3,4-thiadiazines [3] and 3-substituted 2-thioxoimidazolidin-4-ones [4] were prepared via the reaction of 4-substituted benzaldehyde thiosemicarbazones [1] with bromine in AcOH, thioglycolic acid and ethyl chloroacetate in the presence of different bases. Acetylation of 4 with Ac[2]O gave the corresponding monoacetyl derivative [5], while the acetylation of 4 with Ac[2]O in presence of AcONa gave the corresponding diacetyl derivative [6]. 5-Arylidcne-thiazolidine-2,4-diones [8] were synthesized by the reaction of compound 4 with aromatic aldehydes to give 3-substituted 5-arylidene-2-thioxoimid-azolidin-4-ones [7], followed by bromination of 7 in presence of AcONa in acetic acid. The mass spectral fragmentation patterns of some prepared compounds are investigated in order to elucidate the structure of the synthesized compounds
Subject(s)
Sulfur , Thiosemicarbazones , Magnetic Resonance SpectroscopyABSTRACT
Reaction of ethyl beta-[thiophen-2-yl]-alpha-cyanoacrylate I with guanidine hydrochloride and thiosemicarbazide gave the corresponding 2-aminopyrimidine derivative 2 and thiophen-2-yl carboxaldehvde thiosemicarbazone 4. Treatment of 4 with acetic anhydride, benzyl chloride, hydrazine hydrate and bromine solution afforded the corresponding N-diacetyl and N-benzylthiosemicarbazones 5, 6, hydrazone derivative [7] and 1, 2, 4-triazole derivative 8. Acylation of 2 and 8 with acetic anhydride yielded the corresponding N-acetyl derivatives 3 and 9. The mass spectral fragmentation patterns of the some compounds are described
Subject(s)
Thiophenes , Mass Spectrometry , ThiosemicarbazonesABSTRACT
2-[[5-ARYL-THIAZOL-2-YL]-hydrazonomethyl-phenols [2a, b] and 3-[[2-hydroxybenzylidiene]-amino]-2-thioxo-imidazolidin-4-one [3] were prepared via cyclization of salicylaldehydethiosemicarbazone [1] with omega [small latter]-bromomethyl aryl ketones and ethyl chloroacetate in presence of fused sodium acetate. Reaction of 3 with hydrazine hydrate, acetic anhydride, benzaldehyde, ethyl iodide, methyl acrylate and diazonium chloride yielded the corresponding salicylaldazine [4], 1-acetyl-3-[[2-acetoxybenzylidene]-amino]-2-thioxoimidazolidin-4-one [5], 3-[[2-hydroxybenzylidene]-amino]-5-benzylidene-2-thioxo-imidazolidin-4-one [6], 1-substituted-3-[[2-hydroxybenzylidene]-amino]-2-thioxo-imidazolidin-4-ones [8 and 9] and 3-[[5-phenylazo-2-hydroxybenzylidene]-amino]-2-thioxo-imidazolidin-l-one [10]. The mass spectral fragmentation patterns of the compounds are described
Subject(s)
Thiazoles/chemical synthesis , Mass Spectrometry , ThiosemicarbazonesABSTRACT
In laboratory some complexes of platin II, copper II, nikel II with diacetyl monoxin thiosemicarbazon were synthetized. The structure of these complexes and components were determind with UV, UR spectroscopy. The antimiorobial activities were examined on Gram (-) and Gram (+) bacteria, fungi and yeast. Results showed strong antibacterial activities of these synthetized complexes.
Subject(s)
Thiosemicarbazones , Biology , BacteriaABSTRACT
As tiossemicarbazonas constituem classe de compostos que têm apresentado amplo espectro de ação, englobando atividades antibeoplásica, antiinflamatória, tuberculostática e antiviral, inclusive anti-HIV. Diante da potencial atividade antiviral das tiossemicarbazonas, planejamos sintetizar nova série de compostos a partir da tiossemicarbazida e fenoxiacetaldeídos diversamente substituídos. Os produtos obtidos tiveram sua estrutura química comprovada por meio de métodos espectroscópicos no infravermelho e ressonância magnética nuclear de hidrogênio e microanálise. Cinco compostos foram testados visando encontrar possível atividade antiviral. Nos ensaios utilizaram-se culturas de células contínuas VERO e L929 infectadas pelo vírus herpes humano tipo I, da vaccínia, poliomielítico tipo I e da estomatite vesiculosa...
Subject(s)
Antiviral Agents , Phenoxyacetates/chemical synthesis , Thiosemicarbazones/chemical synthesis , Cell Culture Techniques , Magnetic Resonance Spectroscopy/methodsABSTRACT
Este trabalho descreve a síntese e avaliaçäo estrutural de nove tiossemicarbazonas, obtidas pela condensaçäo de ariltioacetaldeídos e artiopropanonas substituídas com cloridrato de tiossemicarbazida. Estes novos compostos foram testados in vitro pelo fitoteste Lepidium sativum. Todos eles apresentaram atividade inibidora do crescimento celular (pI50) superior àquela de 5-fluoruacila, composto anticancerígeno, utilizado como referência.
Subject(s)
Animals , Antineoplastic Agents/chemical synthesis , Growth Inhibitors , In Vitro Techniques , Thiosemicarbazones/chemical synthesis , Aldehydes/pharmacology , Aldehydes/chemical synthesis , Magnetic Resonance Spectroscopy , Semicarbazones/chemical synthesis , Semicarbazones/pharmacology , Spectrophotometry, Infrared , Structure-Activity Relationship , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacologyABSTRACT
A series of quinazolin-4-ones incorporated with pyridones, iminopyridines, thiazole, semicarbazone and thiosemicarbazone moieties were synthesized. Some tested compounds showed considerable biological activity against some microorganisms
Subject(s)
Quinazolines/analogs & derivatives , Antibiosis , Pyridones/chemistry , Pyridines/chemistry , Thiazoles/chemistry , Semicarbazones/chemistry , Thiosemicarbazones/chemistry , Anti-Infective Agents/chemical synthesisABSTRACT
In this study, we tried to establish a relationship between the antioxidant/oxidant property of thiourylene-type compounds and their electrotopological-state [E-state] indexes of thiourylene moiety [SN and S] for different concentrations. Such relationship could be used as a guideline in modulating the immunoregulatory effect prior to the synthesis of new thiourylene-type compounds. The chemiluminescence studies on activated polymorphonuclear leukocytes [PMNLs] were utilized to reveal the antioxidant/oxidant status of a series of thiourylene-type compounds. Results indicate that [1] Not all the thiourylene-type compounds are antioxidants and their antioxidant/oxidant properties varies with the electronic accessibility on the thiourylene moiety as influenced by molecular topology, resonance and steric hindrance by the N-substituents. [2] In case of the compounds containing pure thiourylene moiety, [SN and S] increases with the increase of the oxidant property of the compounds in a linear relationship. [3] In case of compounds such as thiosemicarbazone, electronic accessibility on the S[N and S]and the adjacent nitrogen S[N] was found to be additive and the E-state of S[N and S] + S[N] was related to the oxidant property of the compounds. Thus, emphasizing the importance of thiosemicarbazone moiety in the antithyroid therapy. [4] The antioxidant property of thiourylene-type compounds was reversed at higher concentration with variable magnitude due to the relative accumulation of the stable thiyl pro-oxidant ion. In conclusion, the E-state approach is suitable for establishing guidelines that economize efforts and cost of developing therapeutic agents with the desired immunoregulatory effect
Subject(s)
Luminescent Measurements , ThiosemicarbazonesABSTRACT
A simple, efficient and selective method for the preparation of 2-formylestradiol was described. The methodology involved the use of a modified Sommelet reaction and provided a good yield of pure product, which was characterized by spectroscopy. Then, conversion of the aldehydic group into various thiosemicarbazone moieties was undertaken. Out of the thiosemicarbazone derivatives, the phenylthiosemicarbazone VI exhibited 85% uterotrophic activity relative to estradiol, while the other members of the series showed a weak uterotrophic activity [39-54%] based on dry uterine weight gain. None of the synthesized compounds elicited anti-fertility activity as assessed by the postcoital anti-implantation activity test
Subject(s)
Thiosemicarbazones/analogs & derivatives , Estrogen AntagonistsABSTRACT
The conductance of cobalt [II] complexes of acetone thiosemicarbazone chloride and bromide is measured in methanol-water mixtures covering a dielectric constant ranging between 32.63 - 69.94 at 25C. The data are analyzed using the Fuoss-Onsager equation on an IBM-PC computer. It was found that a degree for chloride increase with the decrease of dielectric constant, while a degree for bromide decreases with the decrease of dielectric constant until a certain value, and then increases thereafter. The plot of log KA vs. 1/D is found to be nonlinear. Finally, the solvent separated-ion pair model is applied to these systems