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INTRODUCTION: Ceramides are known to show anti-cancer activity. A novel ceramide analog, (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide (analog 315) was developed as part of a larger study focused on finding more effective breast cancer treatments. OBJECTIVE: To assess whether analog 315 shows any or a combination of the following effects in breast cancer cells in vitro: inhibiting proliferation, inducing apoptosis, and altering protein expression. Also, to determine whether it inhibits chemo-resistant breast cancer tumor growth in vivo mouse model. METHODS: In vitro cell proliferation and apoptosis after treatment with analog 315 were assessed in three breast cancer cell lines (MCF-7, MCF-7TN-R, and MDA-MB-231) and reported. Protein expression was assessed by microarray assay. For the in vivo studies, chemo-resistant breast cancer cells were used for tumor development in two groups of mice (treated and control). Analog 315 (25â mg/kg/day) or control (dimethyl sulfoxide) was administered intraperitoneally for 7 days. Effects of analog 315 on inhibiting the growth of chemo-resistant breast cancer tumors after treatment are reported. RESULTS: Analog 315 reduced MCF-7TN-R chemo-resistant tumor burden (volume and weight) in mice. Liver metastasis was observed in control mice, but not in the treated animals. Ki-67, a proliferation marker for breast cancer cells, increased significantly ( P â <â 0.05) in control tumor tissue. In vitro studies showed that analog 315 inhibited cell proliferation, altered protein expression and induced apoptosis in all three breast cancer cell lines studied, of which the effects on MCF-7TN-R cells were the most significant. CONCLUSION: Analog 315 reduced tumor growth in chemo-resistant breast cancer, inhibited cell proliferation, altered protein expression, and induced apoptosis in all three cell lines studied.
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Neoplasias da Mama , Ceramidas , Humanos , Animais , Camundongos , Feminino , Ceramidas/farmacologia , Linhagem Celular Tumoral , Células MCF-7 , Dimetil Sulfóxido , Neoplasias da Mama/patologia , Apoptose , Proliferação de CélulasRESUMO
As a potential means for smoking cessation and consequently prevention of smoking-related diseases and mortality, in this study, our goal was to investigate the inhibition of nicotine metabolism by P450 2A6. Smoking is the main cause of many diseases and disabilities and harms nearly every organ of the body. As reported by the Centers for Disease Control and Prevention (CDC), more than 16 million Americans are living with diseases caused by smoking. On average, the life expectancy of a smoker is about 10 years less than a nonsmoker. Smoking cessation can substantially reduce the incidence of smoking-related diseases, including cancer. At least, 70 of the more than 7000 cigarette smoke components, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are known carcinogens. Nicotine is the compound responsible for the addictive and psychopharmacological effects of tobacco. Cytochrome P450 enzymes are responsible for the phase I metabolism of many tobacco components, including nicotine. Nicotine is mainly metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism decreases the amount of available nicotine in the bloodstream, leading to increased smoking behavior and thus exposure to tobacco toxicants and carcinogens. Here, we report the syntheses and P450 2A6 inhibitory activities of a number of new flavone-based esters and acids. Three of the flavone derivatives studied were found to be potent competitive inhibitors of the enzyme. Docking studies were used to determine the possible mechanisms of the activity of these inhibitors.
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Flavonas , Nicotina , Humanos , Nicotina/farmacologia , Nicotina/metabolismo , Citocromo P-450 CYP2A6/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Carcinógenos/metabolismo , Flavonas/farmacologiaRESUMO
Primary effusion lymphoma (PEL) is an aggressive malignancy with poor prognosis even under chemotherapy. Kaposi sarcoma-associated herpesvirus (KSHV), one of the human oncogenic viruses, is the principal causative agent. Currently, there is no specific treatment for PEL; therefore, developing new therapies is of great importance. Sphingolipid metabolism plays an important role in determining the fate of tumor cells. Our previous studies have demonstrated that there is a correlation between sphingolipid metabolism and KSHV+ tumor cell survival. To further develop sphingolipid metabolism-targeted therapy, after screening a series of newly synthesized ceramide analogs, here, we have identified compounds with effective anti-PEL activity. These compounds induce significant PEL apoptosis, cell-cycle arrest, and intracellular ceramide production through regulation of ceramide synthesizing or ceramide metabolizing enzymes and dramatically suppress tumor progression without visible toxicity in vivo. These new compounds also increase viral lytic gene expression in PEL cells. Our comparative transcriptomic analysis revealed their mechanisms of action for inducing PEL cell death and identified a subset of novel cellular genes, including AURKA and CDCA3, controlled by sphingolipid metabolism, and required for PEL survival with functional validation. These data provide the framework for the development of promising sphingolipid-based therapies against this virus-associated malignancy.
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Aurora Quinase A/metabolismo , Ceramidas/farmacologia , Herpesvirus Humano 8/patogenicidade , Linfoma de Efusão Primária/tratamento farmacológico , Sarcoma de Kaposi/complicações , Esfingolipídeos/farmacologia , Animais , Apoptose , Aurora Quinase A/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Sobrevivência Celular , Ceramidas/química , Feminino , Perfilação da Expressão Gênica , Humanos , Linfoma de Efusão Primária/etiologia , Linfoma de Efusão Primária/metabolismo , Linfoma de Efusão Primária/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Sarcoma de Kaposi/virologia , Células Tumorais Cultivadas , Replicação Viral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.
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Cumarínicos/química , Sistema Enzimático do Citocromo P-450/química , Desintoxicação Metabólica Fase I , Xenobióticos/química , Cumarínicos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Xenobióticos/metabolismoRESUMO
The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n=10) were injected bilaterally with 5×10 MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n=5 in each group). The control group mice were injected with 25 µl of dimethyl sulfoxide and the treatment group mice were injected with 10 mg/kg of analog 315 (in dimethyl sulfoxide, 25 µl volume) every day for a period of 3 weeks. Animal weights and tumors were measured every week for 3 weeks. At the end of the experimental period, control animals had retained excess fluid, and showed larger tumor sizes compared with the treated group (2.95 vs. 1.67 g). A 45% reduction in tumor size and 80% decrease in tumor volume were observed in the treatment group. There was a significant increase in the weights of liver (10%) and spleen (19%) between the control and treated animals. Hematoxylin and Eosin staining of MDA-MB-231 tumor sections revealed more acellular necrotic regions in tumors from the treatment groups compared with the ones from the control group. Ki67, a proliferation marker was higher in number in control tumor section (71.8±12.8) compared to the treatment tumor section (37.4±10.4) (P<0.001). Photomicrographs showed metastatic tumor burden in kidney, lungs, and spleen collected from the control group mice bearing MDA-MB-231 tumors. Treatment group mice showed normal microscopic tissue architecture. Overall, our study showed tumor growth inhibition and antimetastatic effects for the novel ceramide analog 315.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ceramidas/farmacologia , Carga Tumoral/efeitos dos fármacos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Ceramidas/química , Dimetil Sulfóxido/administração & dosagem , Feminino , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Renais/prevenção & controle , Neoplasias Renais/secundário , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Metástase Neoplásica/prevenção & controle , Neoplasias Esplênicas/prevenção & controle , Neoplasias Esplênicas/secundário , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We have discovered a transition-metal-free approach to the synthesis of 2,2'-bis(naphthoquinones) using a Diels-Alder reaction of conjugated ketene silyl acetals with benzoquinone. Its monomer analogue can also be synthesized by simply increasing the equivalents of benzoquinone.
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Naftoquinonas , Estrutura Molecular , Naftoquinonas/síntese químicaRESUMO
The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes.
Assuntos
Citocromo P-450 CYP1A1/química , Inibidores do Citocromo P-450 CYP1A2/química , Citocromo P-450 CYP1A2/química , Inativação Metabólica , Citocromo P-450 CYP1A1/antagonistas & inibidores , Humanos , Ligantes , Fígado/enzimologia , Fígado/metabolismo , Modelos Moleculares , Estresse Oxidativo/genética , Especificidade por SubstratoRESUMO
PIM1 is a proto-oncogene encoding the serine/threonine PIM1 kinase. PIM1 kinase plays important roles in regulating aspects of cell cycle progression, apoptosis resistance, and has been implicated in the development of such malignancies as prostate cancer and acute myeloid leukemia among others. Knockout of PIM1 kinase in mice has been shown to be non-lethal without any obvious phenotypic changes, making it an attractive therapeutic target. Our investigation of anthraquinones as kinase inhibitors revealed a series of quinone analogs showing high selectivity for inhibition of the PIM kinases. Molecular modeling studies were used to identify key interactions and binding poses of these compounds within the PIM1 binding pocket. Compounds 1, 4, 7 and 9 inhibited the growth of DU-145 prostate cancer cell lines with a potency of 8.21µM, 4.06µM, 3.21µM and 2.02µM.
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Antineoplásicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Quinonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Estrutura Molecular , Neoplasias da Próstata/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Quinonas/síntese química , Quinonas/química , Relação Estrutura-AtividadeRESUMO
Diacetylene-containing glycolipids are a unique class of compounds that are able to self-assemble and form ordered supramolecular structures. Polymerizable diacetylene glycolipids that can function as low molecular weight gelators are particularly interesting molecules which can lead to stimuli-responsive smart materials. To discover efficient organogelators with built-in functionality that may be useful in sensing local environmental changes, we have synthesized a series of novel diacetylene-containing amide and urea derivatives using D-glucosamine as the starting material. Both amphiphilic and dipolar glycolipids were synthesized, and these compounds are effective gelators for several organic solvents and aqueous solutions. The resulting gels can be cross-linked under 6 W UV light to produce blue or purple polydiacetylene gels. The cross-linked gels obtained from urea derivatives are generally dark blue and exhibit blue to red color transitions upon heating. Compared to the urea derivatives, the analogous diacetylene amides produced blue to deep purple polymerized gels, depending on the structures of the gelators. The morphologies of the gels were characterized by optical microscopy and scanning electron microscopy. Typically, self-assembled fibrous networks were observed. The synthesis and characterization of these polymerizable gelators and their UV-vis absorption upon polymerization are reported.
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The flavone backbone is a well-known pharmacophore present in a number of substrates and inhibitors of various P450 enzymes. In order to find highly potent and novel P450 family I enzyme inhibitors, an acetylene group was incorporated into six different positions of flavone. The introduction of an acetylene group at certain locations of the flavone backbone lead to time-dependent inhibitors of P450 1A1. 3'-Ethynylflavone, 4'-ethynylflavone, 6-ethynylflavone, and 7-ethynylflavone (KI values of 0.035-0.056 µM) show strong time-dependent inhibition of P450 1A1, while 5-ethynylflavone (KI value of 0.51 µM) is a moderate time-dependent inhibitor of this enzyme. Meanwhile, 4'-ethynylflavone and 6-ethynylflavone are highly selective inhibitors toward this enzyme. Especially, 6-ethynylflavone possesses a Ki value of 0.035 µM for P450 1A1 177- and 15-fold lower than those for P450s 1A2 and 1B1, respectively. The docking postures observed in the computational simulations show that the orientation of the acetylene group determines its capability to react with P450s 1A1 and 1A2. Meanwhile, conformational analysis indicates that the shape of an inhibitor determines its inhibitory selectivity toward these enzymes.
Assuntos
Citocromo P-450 CYP1A1/metabolismo , Inibidores Enzimáticos/química , Flavonas/química , Sítios de Ligação , Domínio Catalítico , Citocromo P-450 CYP1A1/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Flavonas/síntese química , Flavonas/metabolismo , Fluorometria , Cinética , Simulação de Dinâmica Molecular , NADP/química , NADP/metabolismoRESUMO
Small molecular gelators are a class of compounds with potential applications for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protected D-glucose and D-glucosamine are well-suited as building blocks for the construction of low molecular weight gelators. To better understand the scope of D-glucosamine derivatives as gelators, we synthesized and screened a novel class of N-acetylglucosamine derivatives with a p-methoxybenzylidene acetal protective group. This modification did not exert a negative influence on the gelation. On the contrary, it actually enhanced the gelation tendency for many derivatives. The introduction of the additional methoxy group on the phenyl ring led to low molecular weight gelators with a higher pH responsiveness. The resulting gels were stable at neutral pH values but degraded in an acidic environment. The release profiles of naproxen from the pH responsive gels were also analyzed under acidic and neutral conditions. Our findings are useful for the design of novel triggered release self-assembling systems and can provide an insight into the influence of the the structure on gelation.
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Non-small cell lung cancer (NSCLC) constitutes the predominant form of lung cancer and stands as the leading cause of cancer-related mortality in the United States. Conventional chemotherapy and radiotherapy yield suboptimal responses in a significant portion of lung cancer patients, resulting in a discouraging 5-year survival rate of approximately 15%. Despite advancements in targeted therapy and immunotherapy, many NSCLC patients exhibit either negligible or partial responses, emphasizing the pressing necessity for the discovery of innovative anti-cancer agents. Our previous study demonstrated that ABC294640, an inhibitor of one of the key enzymes in sphingolipid metabolism, sphingosine kinase 2 (SphK2), displayed anti-NSCLC activities in vitro and in vivo. In the current study, through the screening of a series of newly synthesized ceramide analogs, we have identified new compounds, particularly analogs 403 and 953, that exhibit potent anti-NSCLC activities. These compounds induce significant NSCLC apoptosis by elevating intracellular pre-apoptotic ceramide and dihydro(dh)-ceramide production. Lipidomics analyses further elucidate the alterations in ceramide and dh-ceramide species signature/proportion across different NSCLC cell-lines induced by these novel ceramide analogs. Treatments with ceramide analogs 403 and 953 remarkably inhibit NSCLC progression in vivo without observable toxicity. Collectively, these findings establish a foundation for the development of promising sphingolipid-based therapies aimed at enhancing the prognosis of NSCLC.
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Factor XIIIa (FXIIIa) is a cysteine transglutaminase that catalyzes the last step in the coagulation process. An anion-binding site inhibition of FXIIIa is a paradigm-shifting strategy that may offer key advantages of controlled inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We previously reported a flavonoid trimer-based allosteric inhibitor of FXIIIa with moderate potency and selectivity. To further advance this approach, we evaluated a series of 27 variably sulfonated heparin mimetics against human FXIIIa. Only 13 molecules exhibited inhibitory activity at the highest concentration tested with IC50 values of 2-286 µM. Specifically, inhibitor 16 demonstrated an IC50 value of 2.4 ± 0.5 µM in a bisubstrate, fluorescence-based trans-glutamination assay. It also demonstrated a significant selectivity over other clotting factors including thrombin, factor Xa, and factor XIa as well as other cysteine enzymes including papain and tissue transglutaminase 2. Inhibitor 16 did not affect the viability of three human cell lines at a concentration that is 5-fold its FXIIIa-IC50. The molecule had a very weak effect on the activated partial thromboplastin time of human plasma at a concentration of >700 µM, further supporting its functional selectivity. Importantly, molecule 16 inhibited FXIIIa-mediated polymerization of fibrin(ogen) in a concentration-dependent manner as shown by the gel electrophoresis experiment. Michaelis-Menten kinetics revealed that the molecule competes with the Gln-donor protein substrate, i.e., dimethylcasein, but not with the Lys-donor small substrate, i.e., dansylcadaverine. Molecular modeling studies revealed that this type of molecule likely binds to an anion-binding site comprising the basic amino acids of Lys54, Lys61, Lys73, Lys156, and Arg244 among others. Overall, our work puts forward a new anion-binding site, selective, nontoxic, sulfonated heparin mimetic FXIIIa inhibitor 16 for further development as an effective and safer anticoagulant.
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Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which mol-ecules are related by inversion centers and 21 axes. Multiple C-Hâ¯O weak hydrogen-bonding inter-actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter-sheet inter-actions are a combination of coumarin system π-π stacking and additional C-Hâ¯O weak hydrogen bonds between ethyl acet-oxy groups.
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Factor XIIa (FXIIa) functions as a plasma serine protease within the contact activation pathway. Various animal models have indicated a substantial role for FXIIa in thromboembolic diseases. Interestingly, individuals and animals with FXII deficiency seem to maintain normal hemostasis. Consequently, inhibiting FXIIa could potentially offer a viable therapeutic approach for achieving effective and safer anticoagulation without the bleeding risks associated with the existing anticoagulants. Despite the potential, only a limited number of small molecule inhibitors targeting human FXIIa have been documented. Thus, we combined a small library of 32 triazole and triazole-like molecules to be evaluated for FXIIa inhibition by using a chromogenic substrate hydrolysis assay under physiological conditions. Initial screening at 200 µM involved 18 small molecules, revealing that 4 molecules inhibited FXIIa more than 20%. In addition to being the most potent inhibitor identified in the first round, inhibitor 8 also exhibited a substantial margin of selectivity against related serine proteases, including factors XIa, Xa, and IXa. However, the molecule also inhibited thrombin with a similar potency. It also prolonged the clotting time of human plasma, as was determined in the activated partial thromboplastin time and prothrombin time assays. Subsequent structure-activity relationship studies led to the identification of several inhibitors with submicromolar activity, among which inhibitor 22 appears to demonstrate significant selectivity not only over factors IXa, Xa, and XIa, but also over thrombin. In summary, this study introduces novel triazole-based small molecules, specifically compounds 8 and 22, identified as potent and selective inhibitors of human FXIIa. The aim is to advance these inhibitors for further development as anticoagulants to provide a more effective and safer approach to preventing and/or treating thromboembolic diseases.
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A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.
Assuntos
Óxidos P-Cíclicos/síntese química , Fosfinas/síntese química , Óxidos P-Cíclicos/química , Ligantes , Estrutura Molecular , Fosfinas/química , EstereoisomerismoRESUMO
A solvent- and metal-free process has been developed for the direct methallylboration of ketones employing the stable B-methallylborinane 1, which was accelerated by tertiary alcohols. In the presence of 2.0 equiv of readily available tertiary alcohols such as tert-amyl alcohol, the methallylation products were prepared at room temperature in excellent yields. The salient features of the described process include simple operation, high efficiency, and mild reaction conditions.
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Álcoois/química , Álcoois/síntese química , Boranos/química , Cetonas/química , Estrutura MolecularRESUMO
Background: Many current anti-cancer drugs used to treat breast cancer mediate tumor cell death through the induction of apoptosis. Cancer cells, however, often acquire multidrug-resistance following prolonged exposure to chemotherapeutics. Consequently, molecular pathways involved in tumor cell proliferation have become potential targets for pharmacological intervention. Ceramides are tumor suppressor lipids naturally found in the cell membrane, and are central molecules in the sphingolipid signalling pathway. Methods: Our lab has targeted the ceramide signaling pathway for potential pharmacological intervention in the treatment of breast cancer. Previously, we have shown that certain ceramide analogs have therapeutic potential in the treatment of chemo-sensitive and multidrug-resistant breast cancers. Using the most active analog from our previous studies as the lead compound, new analogs containing a flavone moiety were designed and synthesized. In general, flavone derivatives often show interesting pharmacological properties, and compounds based on these molecules have been found useful in many different therapeutic areas including anti-tumor, anti-coagulants, and anti-HIV therapy. Results: Synthesis and biological evaluation of five new flavonoid ceramide analogs are reported here. These compounds were also shown to be self-fluorescent, which can be useful when investigating their distribution and action in cancer cells. Conclusion: Four out of the five flavone ceramide analogs in this study showed significant anti-proliferation activities in the three cell lines studied, MDA-MB-232, MCF-7, and MCF-7TN-R; some showing varying degrees of selectivity. The mechanisms involved in cell proliferation inhibition are complicated and further studies are needed.
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A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.
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Quinina/química , Sulfonamidas/síntese química , Compostos de Sulfônio/síntese química , Indicadores e Reagentes/química , Estrutura Molecular , Estereoisomerismo , Sulfonamidas/química , Compostos de Sulfônio/químicaRESUMO
Social media has been playing a vital importance in information sharing at massive scale due to its easy access, low cost, and faster dissemination of information. Its competence to disseminate the information across a wide audience has raised a critical challenge to determine the social data provenance of digital content. Social Data Provenance describes the origin, derivation process, and transformations of social content throughout its lifecycle. In this paper, we present a Big Social Data Provenance (BSDP) Framework for key-value pair (KVP) database using the novel concept of Zero-Information Loss Database (ZILD). In our proposed framework, a huge volume of social data is first fetched from the social media (Twitter's Network) through live streaming and simultaneously modelled in a KVP database by using a query-driven approach. The proposed framework is capable in capturing, storing, and querying provenance information for different query sets including select, aggregate, standing/historical, and data update (i.e., insert, delete, update) queries on Big Social Data. We evaluate the performance of proposed framework in terms of provenance capturing overhead for different query sets including select, aggregate, and data update queries, and average execution time for various provenance queries.