RESUMO
Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.
RESUMO
Gaylussacia brasiliensis (Spreng.) Meissn., Ericaceae, is used in folk medicine for treatment of several inflammatory processes and as healing agent. The scope of this work was to evaluate the in vitro antiproliferative activity of crude dichloromethane extract (CHD) and to identify the compound(s) responsible for this activity. CHD was evaluated and showed a concentration dependent inhibition on all cells lines. Therefore CHD was submitted to several classical columns chromatography providing the most active fraction (FC), inhibiting all cells line at 25 µg/mL. FC was further fractionated affording isolated compound 2β, 3β-dihydroxy-urs-12-ene-28-oic acid , identified on basis of 2D-NMR experiments and showed concentration-dependent activity and selectivity for kidney and breast cell lines.
RESUMO
An activity-guided fractionation of Virola sebifera Aubl. methylene chloride-soluble fraction provided novel 3,5-dihydro-2-(1'-oxo-3'-hexadecenyl)-2-cyclohexen-1-one (3), two known lignans (1, 2) and dehydro hexadecanoyl resorcinol (4). Isolation and purification were conducted with the application of column chromatography and structures were assigned by spetral analysis (1D and 2D NMR, HREIMS). Compounds 1-4 were evaluated for cytotoxic activities against human tumour cell lines UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal) and NCI-ADR (breast expressing phenotype multiple drugs resistance) in vitro. The new polyketide (3) showed selectivity against human OVCAR03 and NCI-ADR cell lines, ranging from 2 to 4 microg/mL.
Assuntos
Proliferação de Células/efeitos dos fármacos , Macrolídeos/farmacologia , Myristicaceae/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Células HT29 , Humanos , Macrolídeos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
The total syntheses of (R)-goniothalamin (1), a styryl lactone isolated from several Goniothalamus species, via catalytic asymmetric allylation of alpha-benzyloxyacetaldehyde (2), followed by ring-closing metathesis and Wittig olefination and via catalytic asymmetric allylation of trans-cinnamaldehyde (12), followed by ring-closing metathesis are reported. The antiproliferative activities of (R)-1 and its Z-isomer 10 as well as of the synthetic dihydropyranone intermediates 7 and 8 against eight different cancer cell lines are also described.
Assuntos
Pironas/síntese química , Pironas/farmacologia , Annonaceae/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Pironas/química , EstereoisomerismoRESUMO
Concise total syntheses of (R)- and (S)-argentilactone have been developed via enantioselective catalytic allylation (ECA) and ring-closing metathesis pathways (four steps, 39% overall yield and 82-84% ee) from 2-octynal and their in vitro activity against cancer cells is described.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Lactonas/síntese química , Lactonas/toxicidade , Antineoplásicos/química , Linhagem Celular Tumoral , Feminino , Humanos , Lactonas/química , Masculino , EstereoisomerismoRESUMO
Tamoxifen (TAM) is a non-steroidal anti-estrogen used to treat patients with estrogen receptor-positive breast cancer and as a chemopreventive agent against breast cancer in high risk pre- and post-menopausal women. However, recent studies have shown that tamoxifen causes endometrial and hepatic cancer. In this study, we examined the effects of tamoxifen (5, 10, 25 and 50 microM) on the growth and proliferation of nine tumoral cell lines (UACC62, MCF-7, NCI-460, K-562, OVCAR-03, PC-03, HT-29, 786-0, NCI-ADR) and non-tumoral cell lines (3T3, V79, MDCK, VERO). Chinese hamster lung fibroblasts (V79) were the most sensitive lineage to tamoxifen, with 21.6% of the cells showing apoptosis at 50 microM TAM. Microscopic analysis showed that, the cellular transformation caused by TAM in V79 cells was similar to that seen with 7,12-dimethylbenz(a)anthracene, thus indicating the carcinogenicity of TAM.
Assuntos
Antineoplásicos Hormonais/toxicidade , Transformação Celular Neoplásica , Antagonistas de Estrogênios/toxicidade , Tamoxifeno/toxicidade , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral/ultraestrutura , Proliferação de Células , Cricetinae , Feminino , HumanosRESUMO
Neste trabalho está descrita a avaliação da atividade antiproliferativa in vitro dos extratos e frações da Aspidosperma tomentosum Mart, árvore originária do cerrado, popularmente conhecida como "peroba do campo", sendo seu tronco utilizado como madeira e as sementes utilizadas em trabalhos artesanais. A atividade antiproliferativa foi determinada através do método da sulforrodamina B (SRB), utilizando cinco linhagens tumorais humanas: K-562 (leucemia), MCF 7 (mama), NCI-ADR (mama, expressando fenótipo de resistência a múltipla drogas), NCI-460 (pulmão) e UACC-62 (melanoma). Foram estudadas as atividades antiproliferativas dos extratos dic1orometânico e etanólico da espécie vegetal Aspidosperma tomentosum Mart. Os extratos brutos inibiram, de forma concentração-dependente, o crescimento das linhagensMCF 7, UACC62, NCI-ADR e NCI-460. Comparativamente ao extrato etanólico, o extrato diclorometânico apresentou uma maior atividade antiproliferativa nestas linhagens inclusivecom efeito citocida sobre a linhagemMCF 7, na concentração de 125 ~g / mL . Foi constatado que neste ensaio, os extratos brutos não inibiram significantemente o crescimento da linhagemK-562 na maior concentração utilizada. o extrato diclorometânico bruto foi particionado por cromatografia em coluna seca fornecendo as frações denominadas Fração ApoIar (FA), Fração de média polaridade rica em terpenos (FMT), Fração de média polaridade rica em alcalóides (FMA) e a Fração Polar (FP). FMT diminuiu de forma concentração-dependente o crescimento das inhagens testadas, com maior seletividadepara MCF 7 e NCI-460, enquanto que FP não demonstrou seletividade celular, tendo inibido todas as linhagens de forma concentração-dependente, apresentando efeito citocida na concentração de 125 ~g/mL. As frações FA e FMA não apresentaram inibição significativa nas doses testadas. Estes dados sugerem que o(s) princípio(s) ativo(s) responsável(eis) pela atividade antiproliferativa estão concentrados na FMT
CUITentIy,over a hundred types of cancer are known, differentiated by etiology, natural history and fonn of treatment. Notwithstanding the great evolution of knowledge conceming this type of pathology, such progress has not been reflected in a proportional way in the development of eflicient techniques of prevention and cure. The existence of neoplastic cells which present resistance mechanisms against chemotherapeutic agents and the low selectivity of these pharmaceuticals, resulting in different levels of toxicity to normal tissues, are limitingfactors to the success of the antineoplastic treatment. Therefore, there is a great need for new and better therapeutic resources, including new chemotherapeutic agents. This study evaluated the in vitro ntiproliferativeactivity of crude extracts and ITactionsof Aspidosperma tomentosum Mart, a tree ITomthe so-called cerrado woods, popularly known as "peroba do campo". Antiproliferative activity was determined by the sulforhodamineB assay using five human cancer celllines: K-562 (leukemia), MCF 7 (breast), NCI-ADR (breast expressing the multidrug resistance phenotype), NCI-460 (lung) and UACC-62 (melanoma). Cells were cultured in the presence of the test substance for 48 h. The exposure to dicloromethane and ethanol extracts ITomthe Aspidosperma tomentosum Mart. resulted in concentration-dependent growth inhibition on MCF 7, UACC-62, NCI-ADR and NCI-460. Comparing to the ethanol extract, the dichoromethane extract presented a higher activity on these celllines, including a cytocidal effect against MCF 7 at a concentration of 125!lglrnL.The crude extracts did not significantlyinhibit the growth ofthe K562 at maximum concentration tested. The crude dichoromethane extract was ITactionated by column chromatography on silicagel, providing ITactions denominated: unpolar (FA), terpenic medium polar (FMP), alkaloid medium polar (FMA) and polar ftaction (FP). FMT exposure produced concentration-dependent growth inhibition of...