Browsing by Author "Mafud, Ana Carolina"
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- Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeavesPublication . Rocha, Jefferson A.; Andrade, Ivanilza M.; Véras, Leiz M.C.; Quelemes, Patrick V.; Lima, David F.; Soares, Maria J.S.; Pinto, Pedro L.S.; Mayo, Simon J.; Ivanova, Galya; Rangel, Maria; Correia, Manuela; Mafud, Ana Carolina; Mascarenhas, Yvonne P.; Delerue-Matos, Cristina; Moraes, Josué de; Eaton, Peter; Leite, José R.S.A.Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.
- Copper nanoparticles stabilized with cashew gum: Antimicrobial activity and cytotoxicity against 4T1 mouse mammary tumor cell linePublication . Amorim, Adriany; Mafud, Ana Carolina; Nogueira, Silvania; Ramos-Jesus, Joilson; Araújo, Alyne Rodrigues de; Plácido, Alexandra; Neta, Maria Brito; Alves, Michel Muálem Moraes; Carvalho, Fernando Aécio Amorim; Rufino Arcanjo, Daniel Dias; Braun, Sacha; López, Marta Sánchez-Paniagua; López-Ruiz, Beatriz; Delerue-Matos, Cristina; Mascarenhas, Yvonne; Silva, Durcilene; Eaton, Peter; Leite, José Roberto Souza AlmeidaCopper nanoparticles stabilized with cashew (CG-CuNPs) were synthesized by reduction reaction using ascorbic acid and sodium borohydride, using the cashew gum (CG) as a natural polymer stabilizer. Dynamic light scattering, atomic force microscopy, Fourier-transform infrared spectroscopy, UV-Vis spectrophotometry, and x-ray diffraction were used to characterize the nanoparticles (CG-CuNPs), and copper was quantified by electrochemical measurement. The UV-vis spectra of the CG-CuNPs confirmed the formation of nanoparticles by appearance of a surface plasmon band at 580 nm after 24 h of reaction. The Fourier-transform infrared spectrum of CG-CuNPs showed the peak at 1704 cm−1 from cashew gum, confirming the presence of the gum in the nanoparticles. The average size of CG-CuNPs by dynamic light scattering and atomic force microscopy was around 10 nm, indicating small, approximately spherical particles. Antimicrobial assays showed that CG-CuNPs had activity against Staphylococcus aureus ATCC 29213 with a minimal inhibitory concentration of 0.64 mM. The cytotoxicity assay on BALB/c murine macrophages showed lower cytotoxic effects for CG-CuNPs than CuSO4·5H2O. Viability cell assays for CG-CuNPs at (0.250 mM) inhibited by 70% the growth of 4T1 LUC (4T1 mouse mammary tumor cell line) and NIH 3T3 cells (murine fibroblast cells) over a 24-h period. Therefore, CG-CuNPs can be used as an antimicrobial agent with lower cytotoxic effects than the CuSO4·5H2O precursor.
- In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippiumPublication . Arcanjo, Daniel D. R.; Mafud, Ana Carolina; Vasconcelos, Andreanne G.; Silva-Filho, José Couras da; Amaral, Maurício P. M.; Brito, Lucas M.; Bemquerer, Marcelo P.; Kückelhaus, Selma A. S.; Plácido, Alexandra; Delerue-Matos, Cristina; Vale, Nuno; Mascarenhas, Yvonne P.; Carvalho, Fernando Aécio A.; Oliveira, Aldeidia P.; Leite, José Roberto Souza AlmeidaBPP-BrachyNH2 is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH2. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH2 induced high predicted LD50 values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH2 at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH2, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.
- Structure and function of a novel antioxidant peptide from the skin of tropical frogsPublication . Barbosa, Eder Alves; Oliveira, Ana; Plácido, Alexandra; Socodato, Renato; Portugal, Camila C.; Mafud, Ana Carolina; Ombredane, Alicia S.; Moreira, Daniel C.; Vale, Nuno; Bessa, Lucinda J.; Joanitti, Graziella A.; Alves, Cláudia; Gomes, Paula; Delerue-Matos, Cristina; Mascarenhas, Yvonne Primerano; Marani, Mariela M.; Relvas, João B.; Pintado, Manuela; Leite, José Roberto S.A.The amphibian skin plays an important role protecting the organism from external harmful factors such as microorganisms or UV radiation. Based on biorational strategies, many studies have investigated the cutaneous secretion of anurans as a source of bioactive molecules. By a peptidomic approach, a novel antioxidant peptide (AOP) with in vitro free radical scavenging ability was isolated from Physalaemus nattereri. The AOP, named antioxidin-I, has a molecular weight [M+H]+ = 1543.69Da and a TWYFITPYIPDK primary amino acid sequence. The gene encoding the antioxidin-I precursor was expressed in the skin tissue of three other Tropical frog species: Phyllomedusa tarsius, P. distincta and Pithecopus rohdei. cDNA sequencing revealed highly homologous regions (signal peptide and acidic region). Mature antioxidin-I has a novel primary sequence with low similarity compared with previously described amphibian's AOPs. Antioxidin-I adopts a random structure even at high concentrations of hydrophobic solvent, it has poor antimicrobial activity and poor performance in free radical scavenging assays in vitro, with the exception of the ORAC assay. However, antioxidin-I presented a low cytotoxicity and suppressed menadione-induced redox imbalance when tested with fibroblast in culture. In addition, it had the capacity to substantially attenuate the hypoxia-induced production of reactive oxygen species when tested in hypoxia exposed living microglial cells, suggesting a potential neuroprotective role for this peptide.
- Structure-function studies of BPP-BrachyNH 2 and synthetic analogues thereof with Angiotensin I-Converting EnzymePublication . Arcanjo, Daniel D.R.; Vasconcelos, Andreanne G.; Nascimento, Lucas A.; Mafud, Ana Carolina; Plácido, Alexandra; Alves, Michel M.M.; Delerue-Matos, Cristina; Bemquerer, Marcelo P.; Vale, Nuno; Gomes, Paula; Oliveira, Eduardo B.; Lima, Francisco C.A.; Mascarenhas, Yvonne P.; Carvalho, Fernando Aécio A.; Simonsen, Ulf; Ramos, Ricardo M.; Leite, José Roberto S.A.The vasoactive proline-rich oligopeptide termed BPP-BrachyNH2 (H-WPPPKVSP-NH2) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH2 was investigated in order to predict which structural components are important or required for interaction with ACE. Furthermore, the toxicological profile was assessed by in silico prediction and in vitro MTT assay. Two BPP-BrachyNH2 analogues (des-Trp1-BPP-BrachyNH2 and des-Pro8-BPP-BrachyNH2) were synthesized, and in vitro and in silico ACE inhibitory activity and toxicological profile were assessed. The des-Trp1-BPP-BrachyNH2 and des-Pro8-BPP-BrachyNH2 were respectively 3.2- and 29.5-fold less active than the BPP-BrachyNH2-induced ACE inhibitory activity. Molecular Dynamic and Molecular Mechanics Poisson-Boltzmann Surface Area simulations (MM-PBSA) demonstrated that the ACE/BBP-BrachyNH2 complex showed lower binding and van der Wall energies than the ACE/des-Pro8-BPP-BrachyNH2 complex, therefore having better stability. The removal of the N-terminal tryptophan increased the in silico predicted toxicological effects and cytotoxicity when compared with BPP-BrachyNH2 or des-Pro8-BPP-BrachyNH2. Otherwise, des-Pro8-BPP-BrachyNH2 was 190-fold less cytotoxic than BPP-BrachyNH2. Thus, the removal of C-terminal proline residue was able to markedly decrease both the BPP-BrachyNH2-induced ACE inhibitory and cytotoxic effects assessed by in vitro and in silico approaches. In conclusion, the aminoacid sequence of BPP-BrachyNH2 is essential for its ACE inhibitory activity and associated with an acceptable toxicological profile. The perspective of the interactions of BPP-BrachyNH2 with ACE found in the present study can be used for development of drugs with differential therapeutic profile than current ACE inhibitors.