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A series of arylidene N-alkoxydiketopiperazines was designed and stereoselectively synthesized via oxime-ether formation and intramolecular acylation. Possible cyclization and acid-catalyzed rearrangement-fragmentation mechanisms were discussed. The crystal structure of the novel diketopiperazine further confirmed the rearrangement mechanism. Most compounds exhibited antitumor activity. Several compounds were more potent against caspase-3. Specifically, compounds 6e, 6g, and 6f inhibited caspase-3 at IC50 values lying within the low micromolar range and demonstrated good selectivity. The binding modes of alkoxydiketopiperazines in the active center of caspase-3 were also discussed based on the molecular docking results.
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Antineoplásicos/farmacologia , Caspase 3/metabolismo , Dicetopiperazinas/farmacologia , Inibidores Enzimáticos/farmacologia , Peptídeos Cíclicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Dicetopiperazinas/síntese química , Dicetopiperazinas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/química , Relação Estrutura-AtividadeRESUMO
A novel method combining ultra-high performance liquid chromatography (UHPLC) fingerprint and simultaneous quantitative analysis of eight phenolic components was developed and validated for quality evaluation of Tetrastigma hemsleyanum leaves. For fingerprint analysis, 15 peaks were selected as the common peaks to evaluate the similarities among 41 batches of T. hemsleyanum leaves collected from different regions. Additionally, simultaneous quantification of eight markers, including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoorientin, orientin, vitexin-2-O-rhamnoside,vitexin and isovitexin, was performed and the obtained data demonstrated that our method has achieved desired linearity, precision and accuracy. Clustering statistical analysis was further application in T. hemsleyanum leaves from different regions. The results indicated that new approach conbine ultra-high performance liquid chromatography (UHPLC) fingerprint and simultaneous quantitative analysis of eight phenolic components was applicable in quality control of T. hemsleyanum leaves.
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Fenóis/análise , Folhas de Planta/química , Vitaceae/química , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análiseRESUMO
A series of open-chain analogs of cyclic peptides was designed and synthesized using sansalvamide A as a model compound. All compounds exhibited low antitumor activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH, SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds were potent against protein tyrosine phosphatase Shp2. Specifically, compounds 1a, 1d, 2b, and 2f were found to inhibit SHP2 with IC50 values in the low micromolar range and good selectivity. Based on the molecular docking results, the binding modes of the chain cyclic peptides in the active center of SHP2 were discussed.
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Inibidores Enzimáticos/síntese química , Peptídeos Cíclicos/síntese química , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Acetilcolinesterase/química , Domínio Catalítico , Catepsina B/antagonistas & inibidores , Catepsina B/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios Enzimáticos , Inibidores Enzimáticos/farmacologia , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Expressão Gênica , Células HeLa , Humanos , IMP Desidrogenase/antagonistas & inibidores , IMP Desidrogenase/química , Cinética , Simulação de Acoplamento Molecular , Peptídeos Cíclicos/farmacologia , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Relação Estrutura-AtividadeRESUMO
The study is aimed to understand the resource and the current situation of the use of Cibotii Rhizoma and provide the basis for protecting and utilization. The method of literature survey, field survey and quality assessment were applied in the study. The results showed that all the Cibotii Rhizoma came from wild resource and was mainly founded in Fujian, Guangxi, Guizhou, Yunnan, Guangdong, Hunan, Jiangxi, Sichuan, Chongqing, Zhejiang, etc. It contains over 5 000 000 kg in the area which total is about 7 000 hm2. The annual output is over 850 000 kg. At present, there is no cultivated resources. Based on the investigation and market sampling analysis from various regions, the results showed that the quality of the collected crude drugs conformed with the regulations of the Chinese pharmacopoeia. However the qualification rate of decoction pieces of Cibotii Rhizoma in market was only 56.4%. At present, the resource of Cibotii Rhizoma could meet the needs of medinal uses. It is important to protect the wild resource which is less and less because of the environmental factors. It also need to make a standard of processing method to ensure the safety, and solve quality problem of the decoction pieces.
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Gleiquênias/química , Gleiquênias/crescimento & desenvolvimento , China , Conservação dos Recursos Naturais , Medicamentos de Ervas Chinesas/análise , Controle de Qualidade , Rizoma/química , Rizoma/crescimento & desenvolvimentoRESUMO
In this study, a rapid and sensitive analytical method was developed for the determination of 10 major compounds (procyanidin B1, catechin, procyanidin B2, rutin, isoquercitrin, kaempferol-3-O-rutinoside, astragalin, quercitrin, quercetin, and kaempferol) in Tetrastigma hemsleyanum by using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-MS/MS) in multiple-reaction monitoring (MRM) mode. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 mm x 100 mm, 1.6 µm) with the mobile phase consisting of acetonitrile (A) and 0.1% aqueous formic acid (B) in gradient elution at a flow rate of 0.25 mL · min(-1) and the column temperature was set at 45 °C. Under the optimized chromatographic conditions, good separation for 10 target compounds were obtained including chiral isomer procyanidins B1 and B2 were completely separated within 8.5 min. Satisfactory linearity was achieved with wide linear range and fine determination coefficient (r > 0.996 6), the overall recoveries were ranged from 95.44%-110.40% with the RSD ranging from 2.37%-8.69%. It is the first report about simultaneous analysis of 10 major flavonoids components in Tetrastigma hemsleyanum by using UPLC-MS/MS method, which affords highly sensitive, specific, speedy and efficient method for quality control of Tetrastigma hemsleyanum
Assuntos
Flavonoides/química , Vitaceae/química , Acetonitrilas , Cromatografia Líquida de Alta Pressão , Quempferóis , Quercetina/análogos & derivados , Rutina , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To develop a method for separation and quantitative determination of four flavonoids in Tetrastigma hemsleyanum. METHODS: The Separation was performed on a Waters Preparative scale LC-MS autopurification system. Several spectral analyses, such as NMR,HR-MS and UV were used to identify the chemical structures. Quantitative assay was performed on a UHPLC Phenomenex Kinetex C18 column (100 mm x 4.6 mm, 2.6 µm) with the mobile phase consisting of acetonitrile( B) and water containing 0. 1% formic acid (A) in a gradient mode at a flow rate of 0.4 mL/min. The column temperature was at 30 °C and the optimum detection wavelength of DAD was set at 350 nm. RESULTS: Four flavonoids were isolated from the root of Tetrastigma hemsleyanum, which were identified as rutin, isoquercitrin, kaempferol-3-O-rutinoside and astragalin. As to quantitative analysis, a good separation of four flavonoids with in 17.5 min, the linear range of rutin, isoquercitrin, kaempferol-3-O-rutinoside and astragalin was 0.283-11.32 µg/mL (r1 = 0.9998), 0.311-12.44 µg/mL (r2 = 0.9994), 0.277-11.08 µg/mL (r3 = 0.9995) and 0.103-2.06 µg/mL (r4 = 0.9990), respectively. The average recovery (n = 6) was 99.75% (RSD = 2.15%), 98.73% (RSD = 2.58%) ,98. 03% (RSD = 2.23%), and 97.62% (RSD = 1.95%), respectively. CONCLUSION: Four flavonoids are isolated from the root of Tetrastigma hemsleyanum for the first time, and the UHPLC method is simple, rapid and accurate, which can be used for quantitative analysis of multi-component of Tetrastigma hemsleyanum and provide a novel approach for evaluation of the quality of Tetrastigma hemsleyanum comprehensively.
Assuntos
Flavonoides/química , Vitaceae/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Flavonoides/isolamento & purificação , Quempferóis , Quercetina/análogos & derivados , RutinaRESUMO
A qualitative analytical method of liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) was developed for identification of multi-constituents and an analytical method was developed for simultaneously determining 4 major compounds (rutin, isoquercitrin, kaempferol-3-0-rutinoside, and astragalin) in Tetrastigma hemsleyanum Diels et Gilg. The HPLC-Q-TOF-MS assay was performed on a Welch Ultimate XB-C18 column (4.6 mm x 150 mm, 5 microm) with the mobile phase consisting of acetonitrile (A) and water containing 0.1% Formic acid (B) in gradient mode at a flow rate of 0.8 mL x min(-1). The column temperature was at 30 degrees C, and negative ion mode was used for TOF-MS. The UPLC-QqQ-MS assay was performed on a Waters CORTECS C18 (2.1 mm x 100 mm, 1.6 microm) with the mobile phase consisting of acetonitrile (A) and water containing 0.1% formic acid (B) in gradient mode at a flow rate of 0.25 mL x min(-1). The column temperature was at 45 degrees C, and MRM mode was used for QqQ-MS. Based on the retention time and MS spectra, 24 compounds were identified or tentatively characterized by comparing with reference substances or literatures. For quantitative the linear range of 4 detected compounds were good (r > 0.9966), and the overall recoveries ranged from 98.27% to 101.58%, with the RSD ranging from 3.15% to 5.88%. The results indicated that new approach conbined HPLC-Q-TOF-MS and UPLC-QqQ-MS was applicable in qualitative and quantitative quality control of Tetrastigma hemsleyanum.
Assuntos
Vitaceae/química , Acetonitrilas/química , Cromatografia Líquida de Alta Pressão/métodos , Formiatos/química , Espectrometria de Massas em Tandem/métodos , Água/químicaRESUMO
Background: Cisplatin (CP) is commonly used for the initial treatment of lung adenocarcinoma (LUAD). Resistance to CP has long been recognized as a significant obstacle to achieving improved therapeutic outcomes. Nevertheless, the intricate molecular mechanisms underlying the phenomenon remain incompletely understood. Methods: The present study utilized the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to conduct an analysis of the expression of C-terminal binding protein 2 (CTBP2) in LUAD. The correlation between CTBP2 expression and survival data was investigated by the Kaplan-Meier (K-M) plotter. Subsequently, the roles of CTBP2 in CP resistance were explored by analyzing cell viability, cell apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) in CP-resistant cells (A549/DDP). Results: Our data indicated that the CTBP2 expression in LUAD exhibited a significant increase compared to the non-malignant tissues. CTBP2 overexpression showed a correlation to poor survival. CTBP2 knockdown significantly enhanced cell sensitivity to CP in A549/DDP cells. The underlying mechanism is related to promoting ROS production and decreasing MMP after CP treatment. Conclusions: CTBP2 expression has been identified as a novel biomarker for resistance to CP, and its downregulation has been found to enhance sensitivity to CP. Therefore, CTBP2 can serve as a predictor related to CP resistance and a viable therapeutic target for CP resistance in LUAD.
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We developed a new transient directing group, N-(2-benzoyl-4-chlorophenyl)-1,1,1-trifluoromethanesulfonamide, which can facilitate the γ-monoarylation of free amines containing symmetric γ-C-H bonds. A variety of amines containing symmetric and identical γ-C(sp3)-H and γ-C(sp2)-H reacted with a diverse range of aryl and heteroaryl iodides to provide γ-monoarylated products exclusively.
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BACKGROUND: Pine wilt disease (PWD), a major international quarantined forest pest, causes serious ecological and economic damage to Pinus species in Asia and Europe. In China, PWD has spread northeasterly and northwesterly beyond its original northern limits. Consequently, an evaluation of the insect vector-mediated occurrence and potential diffusion of PWD is needed to identify important transmission routes and control the spread of disease. RESULTS: An optimized MaxEnt model was used to assess the current and future geographical distribution of Bursaphelenchus xylophilus and its insect vectors in China. The predicted suitable area for B. xylophilus colonization is currently 212.32 × 104 km2 and mainly concentrated in Central, East, Southwest and South China, although is anticipated to include the northwestern regions of China in the future. As for the insect vectors, Monochamus alternatus and M. saltuarius are expected to spread toward the northwest and southwest, respectively. The maximum predicted dispersion area of PWD mediated by M. alternatus, M. saltuarius and both species was 91.85 × 104, 218.76 × 104 and 29.99 × 104 km2, respectively, with potential diffusion areas being anticipated to increase in the future. Both the suitable probabilities and areas of B. xylophilus and its insect vectors were found to vary substantially along the latitudinal gradient, with the latitudinal range of these species being predicted to expand in the future. CONCLUSION: This is the first study to investigate the potential diffusion areas of PWD mediated by insect vectors in China, and our finding will provide a vital theoretical reference and empirical basis for developing more effective management strategies for the control of PWD in China. © 2024 Society of Chemical Industry.
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A convenient and efficient trans-stereoselective and ß-regioselective hydroboration of propargyl alcohols was achieved simply with LiOtBu as the base and (Bpin)2 as the boron reagent in dimethyl sulfoxide at room temperature. Both terminal and internal propargyl alcohols with diverse structures and functional groups underwent the transformation smoothly to produce ß-Bpin-substituted (E)-allylic alcohols, of which the synthetic potentials were demonstrated by the downstream conversions of boronate, alkenyl, and hydroxyl groups.
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We determined the complete mitochondrial genome of Thereuopoda clunifera (Chilopoda: Scutigeridae) to clarify the phylogenetic status within Chilopoda. Using Sanger sequencing and next-generation sequencing technologies, the entire mitogenome of T. clunifera was assembled and annotated, with 14,898 bp in length and 37 genes (13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes), which are usually found in arthropod mitogenomes. Only one D-loop contained no repeat element. The base composition of T. clunifera was found to be A + T content of 69.55% and G + C content of 30.45%. The AT-skew of T. clunifera was positive, while the GC-skew was negative. The gene order of T. clunifera was identical to that of Scutigera coleoptrata that has been unique among those so far determined for the Arthropoda. We also performed phylogenetic analyses of 25 Myriapoda species to further explore the taxonomic and evolutionary relationships within Myriapoda and Chilopoda. Phylogenetic analyses supported that the division of Chilopoda into subclasses Notostigmophora and Pleurostigmophora.
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Artrópodes , Genoma Mitocondrial , Animais , Artrópodes/genética , Composição de Bases , Quilópodes , Ordem dos Genes , FilogeniaRESUMO
Accumulating evidence has suggested that long non-coding (lnc)RNAs are widely involved in the progression of multiple diseases, including chronic obstructive pulmonary disease (COPD). The aim of the present study was to explore the function and molecule mechanism of maternally expressed gene 3 (MEG3) in cigarette smoke extract (CSE)-treated 16HBE cells. Cell viability and apoptosis were evaluated using Cell Counting Kit-8 analysis and flow cytometry, respectively. Western blot analysis was carried out to determine the protein levels of Bcl-2, Bax and cleaved caspase-3. ELISA assays were utilized to measure the protein levels of IL-1ß and IL-6 and TNF-α. Cytotoxicity was assessed using a lactate dehydrogenase release assay. The expression levels of MEG3 and microRNA (miR)-181a-2-3p were detected using reverse transcription-quantitative PCR. The interaction between miR-181a-2-3p and MEG3 was predicted using DIANA tools and verified by a dual-luciferase reporter assay and RNA Immunoprecipitation assay. MEG3 expression was enhanced while miR-181a-2-3p abundance was reduced in the serum of patients with COPD and CSE-treated 16HBE cells. MEG3-knockdown or miR-181a-2-3p-overexpression inhibited CSE-induced apoptosis, inflammation and cytotoxicity in 16HBE cells. Moreover, miR-181a-2-3p directly bind to MEG3 and its knockdown reversed the inhibitory effect of MEG3 interference on apoptosis, inflammation and cytotoxicity in CSE-treated 16HBE cells. Overall, MEG3-knockdown suppressed CSE-induced apoptosis, inflammation and cytotoxicity in 16HBE cells by upregulating miR-181a-2-3p, providing a promising therapeutic target for treatment of CSE-induced COPD.
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Holly (Ilex L.) is a woody dioecious genus cultivated as pharmaceutical, ornamentals, and industrial materials. Ilex suaveolens (H. Lév.) Loes is an endemic medicinal holly with a predominant distribution in Mount Huangshan, China. In the present work, the complete plastid genome of I. suaveolens was de novo sequenced by high-throughput sequencing technology. The newly-assembled plastid genome holds 37.6% of the overall GC content and a length of 157,857 bp, comprising a large single-copy (LSC, 87,255 bp), a small single-copy (SSC, 18,398 bp), and a pair of inverted repeat (IRs, 26,102 bp) regions. The plastid genome annotation suggested the presence of a total of 89 protein-encoding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The plastome-mediated phylogenetic topology revealed that I. suaveolens clustered together with I. szechwanenesis and I. viridis in the same clade, and a strong relationship between clades and biogeography was found. These data contribute to the understanding of genetic diversity and conservation study of Ilex in Mount Huangshan.
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Iron-catalyzed direct SN2' dehydroxyboration of allylic alcohols has been developed to access (E)-stereoselective allylboronates. Allylic alcohols with diverse structures and functional groups, especially derived from natural products, underwent smooth transformation. The six-membered ring transition state formed by allylic alcohols and iron-boron intermediate was indicated to be the key component involved in transfer of the boron group, activation of the C-OH bond, and control of the stereoselectivity.
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Xiangshan Bay provides most of the seafood for residents from the southeast coast of China. However, information on the safety of local seafood was not well known. In this study, we investigated the residue, spatial distribution and potential health risks of ten polychlorinated biphenyls (PCBs) in seafood and surface sediment samples during six years (2011-2016). The results indicated the level of PCBs in 9 types of seafood from Xiangshan Bay ranged between ND and 25.3 ng·g-1. The highest average concentration of PCBs (14.2 ng·g-1) was observed in Ostreidae. The average PCB concentrations in the surface sediments was 1.58 ng·g-1 (ND to 15.2 ng·g-1). The biota-sediment accumulation factors of the PCBs in most seafood indicated that the seafood was readily subjected to the bioaccumulation of PCBs from sediments. The carcinogenic risks were all within the safe ranges of 9 types of seafood for adults.
Assuntos
Baías/química , Sedimentos Geológicos/química , Bifenilos Policlorados/análise , Alimentos Marinhos/análise , China , Medição de Risco , Poluentes Químicos da Água/análiseRESUMO
Indigenous animals show unique gut microbiota (GM) in the Tibetan plateau. However, it is unknown whether the hypertensive indigenous people in plateau also have the distinct gut bacteria, different from those living in plains. We sequenced the V3-V4 region of the gut bacteria 16S ribosomal RNA (rRNA) gene of feces samples among hypertensive patients (HPs) and healthy individuals (HIs) from 3 distinct altitudes: Tibetans from high altitude (3600-4500 m, n = 38 and 34), Hans from middle altitude (2260 m, n = 49 and 35), and Hans from low altitude (13 m, n = 34 and 35) and then analyzed the GM composition among hypertensive and healthy subgroups using the bioinformatics analysis, respectively. The GM of high-altitude Tibetan and middle-altitude Han HPs presented greater α- and ß-diversities, lower ratio of Firmicutes/Bacteroidetes (F/B), and higher abundance of beneficial Verrucomicrobia and Akkermansia than the low-altitudes HPs did. The GM of high-altitude Tibetan and middle-altitude HIs showed greater α-diversity and lower ratio of F/B than the low-altitudes HIs did. But, ß-diversity and abundance of Verrucomicrobia and Akkermansia among different subgroups of HIs did not show any differences. Conclusively, the high-altitude Tibetan and middle-altitude Han HPs have a distinct feature of GM, which may be important in their adaptation to hypertension in the plateau environments.
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Savolitinib is a novel small-molecule selective cMet inhibitor. This work characterized its pharmacokinetics in preclinical phase, established the preclinical relationships between PK, cMet modulation and anti-tumor efficacy. In vitro and in vivo animal studies were performed for PK characterization. Savolitinib showed good absorption, moderate tissue distribution, low to intermediate clearance, and low accumulation. Hepatic oxidative metabolism followed by urinary and biliary excretions was the major elimination pathway. Based on preclinical PK data, human PK profiles were predicted using empirical methods. Pharmacodynamic studies for evaluating cMet inhibition and anti-tumor efficacy were conducted in nude mice bearing Hs746t xenograft. PK/PD models were built to link the PD measurements to nude mouse PK. The established integrated preclinical PK/PD model contained a two-compartment non-linear PK model, a biomarker link model and a tumor growth transit model. The IC50 of cMet inhibition and the concentration achieving half of the maximal Hs746t tumor reduction by savolitinib were equal to 12.5 and 3.7â¯nM (free drug), respectively. Based on the predicted human PK data, as well as the established PK/PD model in nude mouse, the human PD (cMet inhibition) profiles were also simulated. This research supported clinical development of savolitinib. Understanding the preclinical PK/PD relationship of savolitinib provides translational insights into the cMet-targeted drug development.
Assuntos
Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/farmacocinética , Pirazinas/farmacologia , Pirazinas/farmacocinética , Triazinas/farmacologia , Triazinas/farmacocinética , Animais , Células CACO-2 , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Modelos Biológicos , Proteínas Proto-Oncogênicas c-met/metabolismo , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro. METHODS: Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5x10(5) or 5x10(6) tumor cells in the right flank, respectively. RESULTS: KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (< or = 1.18 g/kg). No adverse reactions were observed. CONCLUSION: These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Neoplasias Pulmonares/patologia , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Feminino , Flavonoides/isolamento & purificação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Nus , Sarcoma 180/tratamento farmacológico , Células Tumorais CultivadasRESUMO
Melanoma is highly resistant to most traditional treatments; therefore, its incidence and mortality rates are rapidly increasing. The effect of a novel sansalvamide A analogue named LY-15 on the growth and induction of apoptosis in B16 cancer cells was investigated in vitro. The inhibitory effects of LY-15 on B16 cells occurred in a concentration- and time-dependent manner. The B16 cells were cultured in various concentrations of LY-15 (5, 15 and 25 µM), and the ameliorating effect of LY-15 was evaluated using apoptotic protein markers B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and caspase-9. Furthermore, LY-15 effectively inhibited the B16 cell migration, increased the expressions levels of caspase-3, caspase-9 and the pro-apoptotic Bax, and reduced that of the anti-apoptotic Bcl-2. These findings suggested that LY-15 is a promising chemotherapeutic agent against melanoma by inducing apoptosis through the mitochondrial-associated death pathway. In addition, sansalvamide A analogue LY-15 may a significant therapeutic target for the treatment of malignant melanoma cancer.