Navegando por Palavras-chave "Antitumor activity"
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- ItemSomente MetadadadosAnti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins(Elsevier B.V., 2014-09-01) Figueiredo, Carlos R. [UNIFESP]; Matsuo, Alisson L. [UNIFESP]; Massaoka, Mariana H. [UNIFESP]; Polonelli, Luciano; Travassos, Luiz R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Parma; Recepta BiopharmaShort synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light-and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, theyalso exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. in this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. the present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs. (C) 2014 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Avaliação da atividade biológica de metabólitos de Lippia alba (Verbenaceae), Plectranthus amboinicus e Plectranthus barbatus (Lamiaceae)(Universidade Federal de São Paulo, 2016-02-19) Santos, Nara Oshiro dos [UNIFESP]; Sartorelli, Patricia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)This study aimed to identify substances with antimicrobial, antiparasitic and antitumor activities of extract and essential oil from the leaves of Lippia alba (Mill.) N.E. Brown and evaluate the antimicrobial and antitumor activities of essential oils from leaves of Plectranthus amboinicus (Lour.) Spreng and Plectranthus barbatus Andrews. The major compounds identified in the essential oil of L. alba leaves were monoterpenes nerol/geraniol (27%) and neral/geranial (22%), the ketone, 6-methyl-5- hepten-2-one (12%) and sesquiterpene, (E)-caryophyllene (9%). This oil showed cytotoxic activity in vitro against B16F10 (murine melanoma) with IC50 of 45.82 µg/mL. Furthermore, it was found that the oil has antimicrobial activity in vitro, inhibiting Gram-negative bacteria, except Pseudomonas aeruginosa, Gram-positive bacteria and yeasts. The dichloromethane phase obtained from the methanol extract of the leaves of this species showed activity against Leishmania (Leishmania) amazonensis with IC50 of 50.8 µg/mL and among the active groups of fractions were identified triterpenes mixture of oleanolic and ursolic acids, in addition to the steroid stigmasterol, all described in L. alba for the first time. The essential oil from leaves of P. amboinicus presented as major compounds carvacrol (38%), γ-terpinene (15%), (Z)-caryophyllene (14%) and p-cymene (12%), showing cytotoxic activity against B16F10 with IC50 similar to standard drug, however, twice more specific, in addition, showed antimicrobial activity against S. epidermidis, C. albicans, C. neoformans (serotype D), C. gattii (serotypes B and C) and S. cerevisiae. In turn, essential oil from leaves of P. barbatus presentes as major compounds (Z) -caryophyllene (18%), germacrene -D (17%), viridiflorene (14%), cyclosativene (10%) and α -pinene (9%), and has demonstrated activity against C. neoformans (serotype A) and C. gattii (serotype C).
- ItemAcesso aberto (Open Access)Estudo químico e biológico do fungo basidiomiceto Neonothopanus gardneri (Berk. Ex Gardner) e avaliação de plantas com atividade de luciferina fúngica(Universidade Federal de São Paulo, 2017-06-23) Santos, Patricia Dias [UNIFESP]; Sartorelli, Patricia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Basidiomycetes have been widely used in biotechnological processes, mainly due to the production of bioactive polysaccharides. Neonothopanus gardneri (Berk. ex Gardner) is a basidiomycete that can emit light, popularly known as “flor-de-coco”, is found exclusi- vely in South America. The substance responsible for bioluminescence in basidiomycete is 3-hydroxy-hispidin, biosynthesized by hydroxylation of the precursor molecule hispidin, ca- talyzed by hispidin-3-hydroxylase -NAD(P)H-dependent-, resulting in the release of energy in the form of visible and cold light. This substance presents low stability and is accumulated in the basidiomycete in small proportions, once it is consumed during the bioluminescent reaction. To date, no substance with light emission activity from plants has been reported in the literature. Styrylpyrone-class derivatives with a similar structure to hispidin or fungal luci- ferin can be found in several plants, such as Piperaceae, Zingeberaceae and Equisetaceae, and are biosynthesized from reactions catalyzed by styrylpyrone synthase. In this context, it appears as hypothesis of the present work if plants are able to biosynthesize organic com- pounds with light emission activity when hydroxylase and/or luciferase enzymes are exposed in the presence or absence of NAD(P)H. Thus the objective of this study was to evaluate the chemical profile of N. gardneri and the activity of fungal luciferin in ancient, intermediate and recent plant species according to phylogenetic classification. From the 41 species of plants evaluated for fungal luciferin activity, 10 showed light emission in the absence of NAD(P)H, and the species Cattleya sp., Phalaenopsis sp., Casearia sylvestris and Piper tuberculatum showed higher intensity of Light compared to the other species evaluated and compared with the control (3-hydroxy-hispidin). It can be concluded that some vascular plants have luciferin with fungal 3-hydroxy-hispidin activity and react directly with luciferase without the need for addition of NAD(P)H and therefore are capable of emitting light. In addition, the aqueous ex- tract was obtained from N. gardneri mycelia using the solvent accelerated extraction (ASE) technique. From the aqueous extract the polysaccharide fraction was obtained by precipita- tion with ethanol, followed by freezing and thawing processes, Fehling solution precipitation, and dialysis by membranes of different porosities. From these purification steps three dif- ferent polysaccharides were obtained which were then characterized by GC-MS and uni and bidimensional NMR spectroscopy. The main monosaccharide observed was glucose in percentages above 90% in two of them. The glycosidic linkage type wasd 1→6 with β and configurations observed in one of them. The crude extract as well as the fractions obtained during the several steps were also evaluated for cytotoxic activity against four tumor cell li- nes, and no significant activity was observed, suggesting that these polysaccharides may present antitumor activity through other mechanisms.
- ItemAcesso aberto (Open Access)Estudo visando à síntese total de morindaparvina A empregando química de benzino sob condições reacionais brandas(Universidade Federal de São Paulo, 2022-06-22) Souza, Vinícius Vieira de [UNIFESP]; Raminelli, Cristiano [UNIFESP]; http://lattes.cnpq.br/3153931165773039; http://lattes.cnpq.br/3112577874129717A química de benzino tem encontrado diversas aplicações na síntese de produtos naturais e na preparação de materiais funcionais. Dentre os métodos para a geração de benzino e arinos, a reação entre 2-(trimetilsilil)aril trifluorometanossulfonatos e uma fonte de íons fluoreto tem ganhado destaque em química orgânica preparativa. Em conformidade, realizamos um estudo visando à síntese total da antraquinona morindaparvina A, um produto natural com significativa atividade antitumoral, empregando na etapa chave da síntese a reação de anelação de Hauser-Kraus entre 3-cianoftalida e TMS-aril trifluorometanossulfonato, promovida por uma fonte de íons fluoreto. No entanto, a reação de Hauser-Kraus não resultou na morindaparvina A.
- ItemAcesso aberto (Open Access)Estudos de síntese, conformação e atividade biológica de análogos do peptídeo antimicrobiano longipina(Universidade Federal de São Paulo (UNIFESP), 2017-03-31) Silva, Jones Montenegro da [UNIFESP]; Miranda, Antonio de [UNIFESP]; Silva Júnior, Pedro Ismael da; http://lattes.cnpq.br/7158586957386749; http://lattes.cnpq.br/1357848049935882; http://lattes.cnpq.br/4701582072086750; Universidade Federal de São Paulo (UNIFESP)Longipina (Lp) é um potente peptídeo antimicrobiano isolado e caracterizado a partir da hemolinfa do Acustisoma longipe. É rico em lisina (K) e tirosina (Y) e sua sequência primaria é: SGYLPGKYVYKYKGKVF. O objetivo principal deste trabalho é estudar a relação estrutura-atividade de novos análogos da Lp, assim como entender os seus mecanismos de ação. Os peptídeos foram sintetizados pelo método de fase sólida manual e foram purificados e caracterizados por cromatografia líquida de fase reversa e por espectrometria de massas. As atividades antimicrobianas dos peptídeos foram avaliadas através de um ensaio de inibição de crescimento líquido contra P. aeruginosa, E. coli, S. marcescens, E. c1oacae, C. albicans, C. parapsilosis, C. tropicalis, C. neoformans, A. niger, C. herbarum e P. farinosus. As atividades hemolíticas e de resistência à degradação foram feitas, respectivamente, com hemácias e plasma humanos. Após uma análise dos resultados, observamos que os análogos: Ac_[Arg7,12,14,16]_Lp_NH2A,c_[Trp3,9,11,13]_Lp_NH2A;c_[Trp3,9,11,13A, rg7,12,14,16]_ Lp-NH2, Ac-[Des-Ser1, Trp3,9,11,13,Arg7,12,14,16]_Lp_NH2foram os mais ativos quando comparados com a Lp. Até a concentração de 100 IJM todos os compostos testados não apresentaram atividade hemolítica. Os análogos mais ativos foram também os mais resistentes à degradação em plasma. Concluímos que a acetilação e amidação e a substituição dos resíduos de Lys por Arg e de Tyr por Trp geraram análogos mais potentes e menos líticos. As perspectivas futuras são a realização dos estudos conformacionais por dicroísmo circular e a avaliação das atividades antitumorais dos compostos estudados.
- ItemSomente MetadadadosA novel melanoma-targeting peptide screened by phage display exhibits antitumor activity(Springer, 2010-12-01) Matsuo, Alisson L. [UNIFESP]; Tanaka, Aparecida S. [UNIFESP]; Juliano, Maria A. [UNIFESP]; Rodrigues, Elaine G. [UNIFESP]; Travassos, Luiz R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Peptide display on the phage surface has been widely used to identify specific peptides targeting several in vivo and in vitro tumor cells and the tumor vasculature, playing a role in the discovery of bioactive antitumor agents. Bioactive peptides have been selected to target important tumor receptors or apoptosis-associated molecules such as p53. Presently, we attempted to identify potentially antitumor bioactive molecules using the whole cell surface as the recognizable static matrix. Such methodology could be advantageous in cancer therapy because it does not require previous characterization of target molecules. Using a C7C phage display library, we screened for peptides binding to the B16F10-Nex2 melanoma cell surface after pre-absorption on melan-A lineage. After a few rounds of enrichment, 50 phages were randomly selected, amplified, and tested for inhibition of tumor cell proliferation. Seven were active, and the corresponding peptide of each phage was chemically synthesized in the cyclic form and tested in vitro. Three peptides were able to preferentially inhibit the melanoma lineage. A unique peptide, [-CSSRTMHHC-], exhibited in vivo antitumor inhibitory activity against a subcutaneous melanoma challenge, rendering 60% of mice without tumor growth. Further, this peptide also markedly inhibited in vitro and in vivo the tumor cell invasion and cell-to-cell adhesiveness in vitro. This is the first report on a bioactive peptide derived from a C7C library active against whole melanoma cells in vitro and in vivo.
- ItemSomente MetadadadosPlant Proteinases and Inhibitors: An Overview of Biological Function and Pharmacological Activity(Bentham Science Publ Ltd, 2011-08-01) Gomes, Marco T. R.; Oliva, Maria Luiza Vilela [UNIFESP]; Lopes, Miriam Teresa Paz [UNIFESP]; Salas, Carlos E.; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP)Proteinases play a fundamental metabolic role during the life cycle in the plant kingdom. By interacting with endogenous or exogenous inhibitors, the proteolytic activity is modulated to meet metabolic requirements. By probing proteolytic enzymes with their inhibitors, it is possible to identify novel functions unrelated to their proteolytic activity. A group of plant proteolytic enzymes stands as a line of defence against environmental changes as their activation is triggered following various types of stress. On the other hand, plants also contain proteinase inhibitors as countermeasures for their protection against insects and pests. Both proteinases and inhibitors emerge as useful tools to combat human diseases. This review focuses on the biochemical characterization of plant proteinases, their inhibitors, the pharmacological potential of proteinases and inhibitors, and new putative emerging functions of proteolytically inhibited proteinases.
- ItemAcesso aberto (Open Access)Revisão bibliográfica: síntese de derivados de anti-inflamatórios não esteroides (não doadores e doadores de óxido nítrico) e seus mecanismos de ação envolvendo a ciclooxigenase (cox) como agentes antitumorais(Universidade Federal de São Paulo, 2021-12-14) Marcon, Angela Favero [UNIFESP]; Reis, Adriana Karla Cardoso Amorim [UNIFESP]; http://lattes.cnpq.br/8445007688411345; http://lattes.cnpq.br/3967617494306500Os anti-inflamatórios não esteroides (AINEs) são uma classe de anti-inflamatórios de extrema importância no tratamento de sintomas causados por inflamações, sejam elas provocadas por bactérias ou vírus. Eles atuam na inibição da enzima ciclooxigenase (COX), encarregada de produzir prostanoides, principalmente prostaglandinas, substâncias presentes nos tecidos inflamados e que são responsáveis pelos sintomas originados no processo inflamatório. Essa enzima possui duas isoformas conhecidas, sendo uma delas a responsável pela manutenção da integridade da mucosa gastrointestinal (COX-1), enquanto a outra (COX-2) está presente nos tecidos afetados pela inflamação e é responsável pela produção das prostaglandinas presentes neles. Sabendo-se que o câncer é um processo inflamatório e que tecidos afetados por ele expressam a isoforma COX-2, a inibição de COX pode ser de grande ajuda no tratamento dessa patologia. Entretanto, os AINEs não possuem inibição específica, podendo inibir tanto a COX-2 quanto a COX-1, o que dá origem aos efeitos colaterais gastrointestinais ligados ao uso constante de anti-inflamatórios. Nesta revisão bibliográfica, daremos ênfase na busca de artigos, através das plataformas SciFinder e PubMed, que possuam diferentes métodos sintéticos de derivados de AINEs inibidores específicos de COX-2 e não de COX-1, diminuindo seus efeitos colaterais e podendo, assim, serem usados como agentes antitumorais.
- ItemAcesso aberto (Open Access)Síntese, estudos conformacionais e atividade biológica de novos análogos do peptídeo antimicrobiano gomesina(Universidade Federal de São Paulo (UNIFESP), 2016-08-31) Mendes, Roberta Brandao [UNIFESP]; Miranda, Antonio de [UNIFESP]; http://lattes.cnpq.br/1357848049935882; http://lattes.cnpq.br/9759007573287366; Universidade Federal de São Paulo (UNIFESP)Gomesin (ZCRRLCYKQRCVTYCRGR-NH2) is an antimicrobial peptide isolated from hemocytes of the Brazilian spider Acanfhoscurria gomesiana. The molecule has four cysteines that form two intramolecular disulfide bridges at positions 2.15 and 6.11. Gm has a broad spectrum of action and a high toxicity against human erythrocytes. This study aimed to the synthesis of new analogues of gomesin to evaluate their structure-activity and their mechanisms of action in comparison to Gm. Thus, linear and cyclic analogs were synthesized, Ac-Gm2-15, Ac-[D-Lys8]-Gm2-15, Ac-Ifrp", D-Lys8]-Gm2-15, Ac- [Thr2,6,11,15]-Gm2_1A5c, -[ Thr2,6,11,15,D-Lys8]-Gm2_1a5nd Ac-[Thr2,6,11,15,D-Pro9]-Gm2_1b5y using the solid phase peptides synthesis in a t-Boc strategy. Then peptides were cleaved, purified and characterized. Antimicrobial activity were evaluated against C. albicans, B. megaferium, P. aeruginosa, P. expansum, C. neoformans, A. niger, Cladosporium sp and S. cerevisiae; hemolytic activity was determined against human erythrocytes; Peptides degradation resistance in human plasma and antitumoral activity against K562 cells were also evaluated. Structural analysis by Circular Dichroism spectroscopy and peptide/vesicle interaction using giant unilamellar vesicles and optical microscopy were also performed. Thermodynamical studies of the interaction peptide I lipid using large unilamellar vesicles (LUVs) was done by isothermal titration calorimetry (ITC). Our results showed that analogues, Ac-Gm2-15, Ac-[D-Lys8]-Gm2-15 and Ac-IIrp", D-Lys8]-Gm2-15, presented the best antimicrobial activity, particularly against microorganisms A. nigerand S. cerevisiae, their performance were even better than Gm. Ali showed low hemolytic activity even at 100 IJM concentration. They were quite resistant to degradation. Fro the Circular Dichroism studies, we observed that the cyclic compounds showed conformations similar than to gomesin, they also assume a p-hairpin conformation. On the other hand, linear analogues showed a prevalence of random conformation. The Iytic mechanism of action of Gm and Ac-Gm2-15 showed to be very similar, both of them caused a disruption of the membrane. Ac-[Thr2,6,11,15]-Gm2_1p5resented a pore formation mechanism. From our results, we had confirmed the crucial importance of the disulfide bridges in the Iytic mechanism of action; in fact its removal causes a decrease in the antimicrobial, hemolytic and antitumor activities. The disulfide bridges also have a great contribution to the stability and strength the action against plasma protease. Gomesin fragments should have less potency, maybe due to the lower amount of charge and also because of the removal of amino acids in the N- and C-terminal portions