Beta Carbolinas: Estudo Dos Mecanismos De Morte, Proliferação E Diferenciação Em Leucemias E Células-Tronco Leucêmicas.

Acute Myeloid Leukemia (Aml) Is A Type Of Cancer That Arises From The Clonal Expansion Of Myeloid Precursors. One Of The Hypotheses That Has Been Raised In Recent Years To Explain The Origin Of Leukemias Is The Presence Of A Rare Population Within The Tumor, Which Represents A Reservoir Refractory To Therapy, Termed Leukemia Stem Cell (Ctl). Evidence Suggests That Mutations In Stem Cells And Normal Progenitor Cells Lead To The Emergence Of Ctl, And Elimination Of This Population Can Be Considered An Important Target. The Use Of Modern Techniques Such As Combinatorial Chemistry And Molecular Modeling Did Not Abolish The Use Of Traditional Knowledge Associated With Natural Resources. It Is Worth Noting That More Than Half Of All Anti-Murine Medicines Approved Between The Years 1940 And 2006 Were Natural Products, Or Derivatives. Among These Resources, We Can Mention The Beta-Carbolinic Alkaloids, In Particular, The Cantinone And Its Derivatives, Which Have Demonstrated Several Pharmacological Activities, Such AA Leucemia Mieloide Aguda (Lma) É Um Tipo De Câncer Que Surge Pela Expansão Clonal De Precursores Mieloides. Uma Das Hipóteses Que Tem Sido Levantada Nos Últimos Anos Para Explicar A Origem Das Leucemias É A Presença De Uma População Rara Dentro Do Tumor, Que Representa Um Reservatório Refratário À Terapia, Denominada De Célula-Tronco Leucêmica (Ctl). Evidências Sugerem Que Mutações Em Células-Tronco E Células Progenitoras Normais Levam Ao Surgimento Das Ctl, E A Eliminação Dessa População Pode Ser Considerada Um Importante Alvo. O Uso De Técnicas Modernas, Como A Química Combinatória, E A Modelagem Molecular, Não Aboliu O Uso Do Conhecimento Tradicional Associado A Recursos Naturais. Vale Destacar, Que Mais Da Metade De Todos Os Medicamentos Antimurais Aprovados Entre Os Anos De 1940 E 2006 Eram Produtos Naturais, Ou Derivados. Dentre Esses Recursos, Podemos Citar Os Alcaloides Beta-Carbolínicos, Em Especial, A Cantinona E Seus Derivados, Que Demonstraram Possuir Diversas Atividades Farmacológicas Como, AntiDados abertos - Sucupira - Teses e dissertações (2018

Chemodiversity and Anti-Leukemia Effect of Metabolites from <i>Penicillium setosum</i> CMLD 18

Penicillium setosum represents a Penicillium species recently described, with little up-to-date information about its metabolic and biological potential. Due to this scenario, we performed chemical and biological studies of P. setosum CMLD18, a strain isolated from Swinglea glutinosa (Rutaceae). HRMS-MS guided dereplication strategies and anti-leukemia assays conducted the isolation and characterization of six compounds after several chromatographic procedures: 2-chloroemodic acid (2), 2-chloro-1,3,8-trihydroxy-6- (hydroxymethyl)-anthraquinone (7), 7-chloroemodin (8), bisdethiobis(methylthio)acetylaranotine (9), fellutanine C (10), and 4-methyl-5,6-diihydro-2H-pyran-2-one (15). From the assayed metabolites, (10) induced cellular death against Kasumi-1, a human leukemia cell line, as well as good selectivity for it, displaying promising cytotoxic activity. Here, the correct NMR signal assignments for (9) are also described. Therefore, this work highlights more detailed knowledge about the P. setosum chemical profile as well as its biological potential, offering prospects for obtaining natural products with anti-leukemia capabilities

Antimicrobial and antileukemic effects: in vitro activity of Calyptranthes grandifolia aqueous leaf extract

Natural products are still a promising source of bioactive molecules. Food and Drug Administration data showed that approximately 49% of the approved molecules originate naturally or chemicallyresemble these substances, of which more than 70% are being used in anticancer therapy. It is noteworthy that at present there are no scientific studies to prove the effectiveness and safety of a number of plants used in folk medicine such as in the case of Calyptranthes grandifolia O. Berg (Myrtaceae) originally from South America. The aim of the present study was to determine the biological potential and toxicological effects of the aqueous leaf extract of C. grandifolia. The main detected phytoconstituents were condensed tannins and flavonoids and a high quantity of polyphenols. Regarding the antimicrobial potential, the extract exerted inhibitory activity against Pseudomonas aeruginosa. The results also revealed the extract induced DNA damage in a concentration-dependent manner in RAW 264.7 cells. In addition, C. grandifolia produced cytotoxicity in leukemia cell lines (HL60 and Kasumi-1) without affecting isolated human lymphocytes but significantly inhibited JAK3 and p38α enzyme activity. Taken together, these findings add important information on the biological and toxicological effects of C. grandifolia, indicating that aqueous extract may be a source of natural antimicrobial and antileukemic constituents.info:eu-repo/semantics/publishedVersio

Cell death profile after treatment with IC₅₀ of the ExEP-P and ExEP-A.

<p>(A) Dot plots indicating the flow cytometry, and (B) representative diagrams obtained via flow cytometry of cells stained with annexin V-FITC/PI; Anx^–/PI^–: viable cells; Anx⁺/PI^–: apoptotic cells; Anx^–/PI⁺: necrotic cells, and Anx⁺/PI⁺: cells in late apoptosis. ***p < 0.001 treated group versus control viable cells. ^###p < 0.001 treated group versus control apoptosis. ⁺⁺⁺p < 0.001 treated group versus control necrosis. ^xxxp < 0.001 and ^xp < 0.05 treated group versus control late apoptosis.</p

Effect of a necrosis inhibitor necrostatin-1 (NEC-1) on cell death mediated by ExEP-P and ExEP-A.

<p>*** p<0.0001 compared with the control group. # p<0.05 NEC-1+ ExEP-P compared with the ExEP-P.</p

DPPH free radical-scavenging activity (%) of ExEP at different concentrations (μg/mL).

<p>DPPH free radical-scavenging activity (%) of ExEP at different concentrations (μg/mL).</p

Antioxidant and cytotoxic activity of propolis of <i>Plebeia droryana</i> and <i>Apis mellifera</i> (Hymenoptera, Apidae) from the Brazilian Cerrado biome - Fig 3

<p>Cytotoxic activity of ExEP from (A) <i>P</i>. <i>droryana</i> and (B) <i>A</i>. <i>mellifera</i> against the peripheral blood mononuclear cells (PBMC) and K562 erythroleukemia cell lines.</p

Viability of K562 cells at 0, 4, 8, 24 and 48 h after treatment with IC₅₀ of the ExEP-P or ExEP-A.

<p>Images are representative of those seen from at least three such fields of view per sample and three independent repeats.</p

Compounds identified in nonpolar fraction of ExEP from <i>P</i>. <i>droryana</i> (ExEP-P) and <i>A</i>. <i>mellifera</i> (ExEP-A) by gas chromatography−mass spectrometry (GC-MS).

<p>Compounds identified in nonpolar fraction of ExEP from <i>P</i>. <i>droryana</i> (ExEP-P) and <i>A</i>. <i>mellifera</i> (ExEP-A) by gas chromatography−mass spectrometry (GC-MS).</p

Image_2_First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin.TIF

The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg.ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg.ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.</p