RESUMO
Despite recent advances in our understanding of the biological processes leading to the development and progression of cancer, there is still a need for new and effective agents to treat this disease. Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are non-enzymatically oxidized products of α-linolenic acid that are present in seeds and vegetable oils. They have been shown to possess anti-inflammatory and apoptosis-promoting activities in macrophages and leukemia cells, respectively. In this work, seven PhytoPs (PP1-PP7) and one PhytoFs (PF1) were evaluated for their cytotoxic, chemosensitization, and anti-migratory activities using the MCF-7 and MDA-MB-231 breast cancer cell lines. Among the tested compounds, only three PhytoPs had a significant effect on cell viability compared to the control group: Ent-9-L1-PhytoP (PP6) decreased cell viability in both cell lines, while 16-F1t-PhytoP (PP1) and 9-L1-PhytoP (PP5) decreased viability of MCF-7 and MDA-MB-231 cells, respectively. When combined with a sub-cytotoxic dose of doxorubicin, these three PhytoPs displayed significantly enhanced cytotoxic effects on MCF-7 cells while the chemotherapeutic drug alone had no effect. In cellular motility assays, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF could significantly inhibit cellular migration of MDA-MB-231 cells. In addition, Ent-9-(RS)-12-epi-ST-Δ10-13-PhytoF also enhanced cellular adhesion of MDA-MB-231 cells.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Furanos/farmacologia , Ácidos Prostanoicos/farmacologia , Ácido alfa-Linolênico/química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Furanos/química , Humanos , Células MCF-7 , Oxirredução , Ácidos Prostanoicos/químicaRESUMO
Enantiopure stereomers of rosaprostol 1, an antiulcer drug, were synthesized from diastereomeric building blocks (-)-5a and (+)-5b. Conversion of (-)-5a into rosaprostol stereomer (-)-(1S,2R,5R)-1a was accomplished in nine steps in 18% overall yield. In this sequence, fully diastereoselective hydrogeneration of the endocyclic carbon double bond in the cyclopentenone ring was key, generating a new stereogenic center (C-2 in 1a). C-5 epimeric rosaprostol (-)-(1S,2R,5S)-1b was obtained from (-)-1a in 72% yield by a two-reaction sequence involving methylation and one-pot Mitsunobu esterification-hydrolysis.
Assuntos
Ácidos Prostanoicos/síntese química , Esterificação , Hidrólise , Estrutura Molecular , Ácidos Prostanoicos/química , EstereoisomerismoRESUMO
Novel 9,11-ethano analogues of prostaglandin endoperoxides with a nitrogen in position 13 were synthesized. (1)H NMR spectra of the obtained compounds were studied. All prostanoids administered perorally at doses of 2.5-10.0 microg x kg(-1) had specific dose-dependent effects on the B-cellular immunity estimated under in vivo conditions on the model of the B-cellular immune response. In terms of the direction of their activities, eight of the studied compounds were found to be immunostimulators, whereas other three compounds displayed immunosuppressing effect. Two of the compounds increased the amount of antibody-forming cells (AFC) per 10(6) spleen cells by 1.9 times in comparison with the respective parameter of control group.
Assuntos
Linfócitos B/imunologia , Ácidos Prostanoicos/síntese química , Ácidos Prostanoicos/farmacologia , Animais , Linfócitos B/efeitos dos fármacos , Compostos Bicíclicos com Pontes/química , Relação Dose-Resposta a Droga , Feminino , Hidrogênio/química , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Camundongos Endogâmicos CBA , Estrutura Molecular , Endoperóxidos de Prostaglandina/química , Ácidos Prostanoicos/química , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologiaRESUMO
[reaction--see text] A new strategy for the synthesis of 2,3-disubstituted cyclopentenones emerges from two key reactions-the ruthenium-catalyzed three-component coupling of an equivalent of HBr, an alkyne, and a vinyl ketone and the Ni-Cr Barbier type reaction. As a result, these important structures are readily accessed from an alkyne and a vinyl ketone (which derive directly from carboxylic acids). Syntheses of tetrahydrodicranenone B and rosaprostol illustrate the new strategy.
Assuntos
Ciclopentanos/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antiulcerosos/síntese química , Antiulcerosos/química , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/química , Bryopsida/química , Ciclopentanos/síntese química , Ésteres/síntese química , Ésteres/química , Expectorantes/síntese química , Expectorantes/química , Fármacos Gastrointestinais/síntese química , Fármacos Gastrointestinais/química , Prostaglandinas Sintéticas/síntese química , Prostaglandinas Sintéticas/química , Ácidos Prostanoicos/síntese química , Ácidos Prostanoicos/químicaRESUMO
The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of arachidonic acid. This review summarizes our current knowledge regarding these compounds. Novel aspects of the biochemistry and bioactivity of IsoPs are detailed and methods by which these compounds are analyzed are discussed. A considerable portion of this review deals with the utility of measuring IsoPs as markers of oxidant injury in human diseases particularly in association with risk factors that predispose to atherosclerosis, a condition in which excessive oxidative stress has been causally implicated.