Abstract Pyrostegia venusta (Ker Gawl.) Miers, popularly known as “Cipó-de São-João”, has been used in traditional medicine for its therapeutic properties. Nanotechnology is able to enhance the pharmacological activity of plant extracts. In this context, liposomes and polymeric nanoparticles containing P. venusta ethanolic extract were developed and then physico-chemically characterized to evaluate the mutagenic/antimutagenic effects of P. venusta. In addition, transaminases and serum creatinine were biochemically analyzed for liver and renal damage, respectively. The micronucleus test was performed with male Swiss mice treated orally for 15 consecutive days with free extracts and nanostructured with P. venusta, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg/kg) on the 15th day of treatment. Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. There was a significant reduction in the frequency of MNPCE (LPEPV = 183% and NPEPV = 114%, p < 0.001), indicating antimutagenic potential of the nanostructured extracts with P. venusta. The groups treated with only nanostructured extract did not show an increase in MNPCE frequency, and biochemical analyzes showed no significant difference between treatments. The liposomes and polymeric nanoparticles containing Pyrostegia venusta ethanolic extract showed biological potential in preventing the first step of carcinogenesis under the experimental conditions.

Abstract Background: The resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. Methods: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Results: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 μM to 19.11 μM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.

RESUMO A secreção cutânea de anuros da família Bufonidae tem grande potencial na busca de novos compostos ativos para utilização como fármacos candidatos no tratamento de algumas doenças, entre elas o câncer. Neste contexto, este estudo teve como objetivo avaliar a atividade citotóxica e antimutagênica dos extratos da secreção da glândula parótida de Rhinella marina e Rhaebo guttatus, bem como a análise bioquímica de transaminases e creatinina séricas, para avaliar dano hepático e renal, respectivamente. A avaliação de citotoxicidade foi realizada pelo método colorimétrico baseado no MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide), com diferentes concentrações dos extratos em culturas de células do Tumor de Walker ou células esplênicas de rato e camundongo. O teste do micronúcleo foi realizado com camundongos Swiss machos que receberam tratamento oral com os extratos durante 15 dias, seguido de tratamento intraperitoneal com N-etil-N-nitrosuréia (50 mg kg-1). A frequência de eritrócitos policromáticos micronucleados (PCEMN) foi determinada em medula óssea. Os extratos apresentaram ação citotóxica nas células avaliadas. Houve uma redução significativa na frequência de PCEMN (R. marina = 56% e R. guttatus = 75%, p < 0,001), observando-se um potencial antimutagênico dos extratos. Os grupos tratados somente com os extratos apresentaram um aumento na frequência de PCEMNs, evidenciando um potencial mutagênico. As análises bioquímicas não apresentaram diferença significativa entre os tratamentos. Assim, nas condições experimentais testadas, as secreções cutâneas de R. marina e R. guttatus apresentaram potencial quimiopreventivo para câncer.

ABSTRACT The skin secretion from toads of the Bufonidae family has great potential in the search for new active compounds to be used as drug candidates in treating some diseases, among them cancer. In this context, this study aimed to evaluate the cytotoxic and antimutagenic activity of the parotoid gland secretion extracts of Rhinella marina and Rhaebo guttatus, as well as biochemically analyze transaminases and serum creatinine for liver and renal damage, respectively. Cytotoxicity was performed by the colorimetric method based on MTT (3- [4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide) with different concentrations of the extracts in Walker or splenic tumor cell cultures from rats and mice. The micronucleus test was performed with male Swiss mice treated orally with the extracts for 15 days, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg kg-1). Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. The extracts showed cytotoxic activity in the evaluated cells. There was a significant reduction in the frequency of MNPCE (R. marina = 56% and R. guttatus = 75%, p < 0.001), indicating antimutagenic potential of the extracts. The groups treated only with extract showed an increase in MNPCE frequency, evidencing mutagenic potential. Biochemical analyzes showed no significant difference between treatments. Thus, under our experimental conditions, the extracts of R. marina and R. guttatus skin secretions presented chemopreventive potential for cancer.

A tea made with the leaves or stem bark of Bauhinia pulchella Benth (Fabaceae) is used in the treatment of diabetes. Ethanol (EEF) and aqueous (EAF) extracts were obtained from the leaves and the antioxidant and citotoxic activities were tested, as well as quantify the content of flavonoids and phenolic compounds (TPC). EEF and EAF showed similar profiles by HPLC, with the presence of three compounds. Column chromatography reverse phase (C18) and Sephadex LH-20, followed by semi preparative HPLC-C18 of EAF resulted in three flavonoids. Their structures were identified by 1H and 13C NMR as myricitrin (1), quercitrin (2) and afzelin (3). In assay of determination of reactive substances to thiobarbituric acid (TBARS), with DPPH, ABTS and nitric oxide (NO•) free radicals, EAF showed antioxidant potential higher than the EEF. This is the first report of the occurrence of the flavonoids 1-3, in the species B. pulchella. EEF and EAF were inactive in the cytotoxicity assays. In short, the polar extracts from the leaves of B. pulchella proved to be promising sources of biomolecules phenolic, with antioxidant potential, which may, in the future, be used as chemical markers for species and validation of therapeutic use.

ABSTRACT Chemical investigation of the leaves of Casearia gossypiosperma Briq., Salicaceae, led to the isolation of two known flavonoids, (+)-taxifolin and quercetin, the leaves of Casearia decandra Jacq. have afforded hydroquinone, the leaves of Casearia rupestris Eichler and Casearia lasiophylla Eichler have afforded a diterpene, (E)-phytol, and the leaves of C. rupestris and Casearia obliqua Spreng. have afforded sitosterol. The twigs of Casearia lasiophylla Eichler led to the isolation of two compounds (+)-pinoresinol, and N-trans-feruloyltyramine, and the twigs of C. obliqua have afforded N-trans-feruloyltyramine, N-trans-cumaroyltyramine, and cinamic acid. This is the first report of the compounds (+)-taxifolin, quercetin, hydroquinone, (+)-pinoresinol and N-trans-cumaroyltyramine from the Casearia genus.

Phytochemical investigation of ethanolic leaves extracts of T. fagifolia led to the isolation of (+)-catechin, sitosterol-3-O-β-D-glucopyranoside, α- and β-tocopherol, a mixture of lupeol, α- and β-amyrin, sitosterol and a mixture of glicosid flavonoids (CP-13). The structures of these compounds were identified by ¹H and 13C NMR spectral analysis and comparison with literature data. Absolute configuration of the catechin was determinate by circular dichroism. Antioxidant activity (EC50), evaluated by 2,2-diphenyl-1-picrylhidrazyl (DPPH) assay system, decreased in the order: (+)-catechin > hydroalcoholic fraction > CP-13 > aqueous fraction > EtOH extract.

Phytochemical investigation from leaves of the Qualea grandiflora (Vochysiaceae) resulted in the isolation and identification of kaempferol-3-O-α-L-(4"-E-p-coumaroyl)-rhamnoside, kaempferol-3-O-α-L-(4"-Z-p-coumaroyl)-rhamnoside, squalene, phytol, lupeol, α-amyrin, β-amyrin, sitosterol, sitostenone, sitosterol-3-O-β-D-glucopyranoside, ursolic and oleanolic acids. The structures of the compounds were identified by 1D- and 2D-NMR experiments, mass and UV spectrometry and comparison with literature data.

The use of natural products to demonstrate the silica gel column chromatography technique is proposed in the present article. It describes the separation of the triterpenes alpha- and beta-amirin from the diol breine and maniladiol, obtained from almécega resin (Protium heptaphyllum March.). The experiment uses an accessible material, was accomplished in 4 h, and can be applied with success an the experimental course of organic chemistry for undergraduate students.

This paper describes the isolation of the furanocassane-type diterpene, named vinhaticoic acid, along with beta-farnesene and spatulenol from fruit shells of D. lacunifera. Structural determinations were accomplished by chemical derivatization and spectral analysis, including 1D and 2D NMR and X-ray crystallography. The fatty portion was extracted from the fruit kernels, transesterfied and analysed by HRGC/MS. Oleic acid (75.8 ± 4.3%) was the major component. Essential oil extracted from the fruit shells of D. lacunifera was analysed by HRGC/MS and nine sesquiterpenes were identified; beta-farnesene (48.6%) and spatulenol (21.61%) were the major constituents.

Three mixtures of triterpenes (maniladiol and breine; alpha and beta-amyrin; lupenone, alpha and beta-amyrinone) were isolated from Protium heptaphyllum March resin. The structural identification was based on NMR and mass spectrometry data. Lupenone, and alpha and beta-amyrinone were not reported before as constituents of this resin. The resin was submitted to methylation and acetylation reactions. The pure and derivatized resins and the mixtures (maniladiol and breine; alpha and beta-amyrin) were analyzed by TG and DSC. The TG curves revealed that the derivatization decreases the thermal stability of the resin. The DSC curves showed peaks that can be assigned to evaporation and phase transitions processes.