Chrysin bonded to ß-d-glucose tetraacetate enhances its protective effects against the neurotoxicity induced by aluminum in Swiss mice.

OBJECTIVES: To evaluate whether the glycosylation of chrysin (CHR) enhances its protective effects against aluminum-induced neurotoxicity. METHODS: To compare the antioxidant, anticholinesterase, and behavioral effects of CHR with its glycosylated form (CHR bonded to ß-d-glucose tetraacetate, denoted as LQFM280), we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (aluminum-induced neurotoxicity in Swiss mice) models. KEY FINDINGS: LQFM280 demonstrated higher antioxidant activity than CHR in both models. Specifically, LQFM280 exhibited the ability to exert antioxidant effects in the cytoplasm of SH-SY5Y cells, indicating its competence in traversing neuronal membranes. Remarkably, LQFM280 proved more effective than CHR in recovering memory loss and counteracting neuronal death in the aluminum chloride mice model, suggesting its increased bioavailability at the brain level. CONCLUSIONS: The glycosylation of CHR with ß-d-glucose tetraacetate amplifies its neuroprotective effects, positioning LQFM280 as a promising lead compound for safeguarding against neurodegenerative processes involving oxidative stress.

Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity.

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5 µM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 µM.

LQFM289: Electrochemical and Computational Studies of a New Trimetozine Analogue for Anxiety Treatment.

This study employs electrochemical and Density Functional Theory (DFT) calculation approaches to investigate the potential of a novel analogue of trimetozine (TMZ) antioxidant profile. The correlation between oxidative stress and psychological disorders indicates that antioxidants may be an effective alternative treatment option. Butylatedhydroxytoluene (BHT) is a synthetic antioxidant widely used in industry. The BHT-TMZ compound derived from molecular hybridization, known as LQFM289, has shown promising results in early trials, and this study aims to elucidate its electrochemical properties to further support its potential as a therapeutic agent. The electrochemical behavior of LQFM289 was investigated using voltammetry and a mechanism for the redox process was proposed based on the compound's behavior. LQFM289 exhibits two distinct oxidation peaks: the first peak, Ep1a ≈ 0.49, corresponds to the oxidation of the phenolic fraction (BHT), and the second peak, Ep2a ≈ 1.2 V (vs. Ag/AgCl/KClsat), denotes the oxidation of the amino group from morpholine. Electroanalysis was used to identify the redox potentials of the compound, providing insight into its reactivity and stability in different environments. A redox mechanism was proposed based on the resulting peak potentials. The DFT calculation elucidates the electronic structure of LQFM289, resembling the precursors of molecular hybridization (BHT and TMZ), which may also dictate the pharmacophoric performance.

Posts Supporting Anti-Environmental Policy in Brazil are Shared More on Social Media.

Weakening environmental laws supported by disinformation are currently of concern in Brazil. An example of disinformation is the case of the "firefighter cattle". Supporters of this idea believe that by consuming organic mass, cattle decrease the risk of fire in natural ecosystems. This statement was cited by a member of the Bolsonaro government in response to the unprecedented 2020 fires in the Pantanal, as well as in support of a new law that enables extensive livestock in protected areas of this biome. By suggesting that grazing benefits the ecosystem, the "firefighter cattle" argument supports the interests of agribusiness. However, it ignores the real costs of livestock production on biodiversity. We analysed the social repercussion of the "firefighter cattle" by analysing public reactions to YouTube, Facebook, and Google News posts. These videos and articles and the responses to them either agreed or disagreed with the "firefighter cattle". Supportive posts were shared more on social media and triggered more interactions than critical posts. Even though many netizens disagreed with the idea of "firefighter cattle", it has gone viral, and was used as a tool to strengthen anti-environmental policies. We advocate that government institutions should use resources and guidelines provided by the scientific community to raise awareness. These materials include international reports produced by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the Intergovernmental Panel on Climate Change (IPCC). We need to curb pseudoscience and misinformation in political discourse, avoiding misconceptions that threaten natural resources and confuse global society.

Indirect evidence of following association between golden dorados (Salminus brasiliensis) and green anacondas (Eunectes murinus) in a Clearwater river of Midwest Brazil / Evidência indireta de associação de seguidor entre dourado (Salminus brasiliensis) e sucuri-verde (Eunectes murinus) em um rio de águas claras do Centro-Oeste do Brasil

Abstract On four occasions, the golden dorado (Salminus brasiliensis) was recorded following the green anaconda (Eunectes murinus) in a clearwater river of Midwest Brazil. These observations were considered as an indirect evidence of a following association known as "nuclear-follower feeding association", a condition in which the follower approach the nuclear when it somehow disturbs the substrate and form sediment clouds while foraging, taking the opportunity to feed during this situation. However, no direct observations of golden dorados getting some benefit from the activity of the green anacondas to feed were made. Nevertheless, as there is a varied list of vertebrates considered as nuclear species in the clearwater rivers of Midwest Brazil, it is to be expected that future observations may provide unusual information about nuclear-follower feeding association between fish and snakes in the Neotropics.

Resumo Em quatro ocasiões, o dourado (Salminus brasiliensis) foi registrado seguindo a sucuri-verde (Eunectes murinus) em um rio de águas claras do Centro-Oeste do Brasil. Essas interações foram consideradas como uma evidência indireta de uma associação de seguidor conhecida como "associação de alimentação nuclear-seguidor", uma condição na qual o seguidor se aproxima da espécie nuclear quando esta de alguma forma perturba o substrato e/ou forma nuvens de sedimentos enquanto forrageia, aproveitando a oportunidade para se alimentar durante essa situação. No entanto, observações diretas de dourados obtendo algum benefício da atividade das sucuris para se alimentar não foram feitas. No entanto, como há uma lista variada de vertebrados considerados como espécies nucleares nos rios de águas claras do Centro-Oeste do Brasil, é de se esperar que observações futuras possam fornecer informações incomuns sobre associações do tipo "nuclear-seguidor" entre peixes e serpentes na região Neotropical.

Enhancing the Luminescence of Eu(III) Complexes with the Ruthenocene Organometallic Unit as Ancillary Ligand.

Five novel Eu(III)-ß-diketonate complexes containing ruthenocene ancillary ligands (1,1'-bis(diphenylphosphoryl)ruthenocene─RcBPO) were synthesized and characterized. The coordination compounds presented the general formula [Eu(ß-dik)3(RcBPO)], where ß-dik stands for 2-thenoyltrifluoroacetonate (tta), 3-benzoyl-1,1,1-trifluoroacetone (btf), 2-dibenzoylmethanate (dbm), 2-acetyl-1,3-indandionate (aind), and 2-benzoyl-1,3-indandionate (bind), and RcBPO stands for 1,1'-bis(diphenylphosphoryl)ruthenocene. The [Eu(aind)3(RcBPO)] complex crystallizes in a monoclinic Cc non-centrosymmetric space group with the europium site environment, assuming a bicapped trigonal prism coordination polyhedron with the symmetry point group close to C2v. Photoluminescent properties for the solid-state samples were described in terms of excitation, emission, lifetime decay curves, and intrinsic and overall quantum yields. The replacement of the two coordinated H2O molecules by the RcBPO ancillary ligand leads to great enhancements of the overall quantum yields (QEuL), with the minimum increment by a factor of 5 for the case of [Eu(btf)3(RcBPO)] and the maximum enhancement of 270 times for the case of the [Eu(dbm)3(RcBPO)] complex. In addition, theoretical calculations were carried out to model the spectroscopic properties of the investigated compounds. To obtain theoretical Judd-Ofelt parameters (Ωλ, λ = 2, 4, and 6) and intramolecular energy transfer rates, the JOYSpectra web platform was employed using the structure obtained from density functional theory calculations. Hence, a rate equation model provided theoretical overall quantum yields, which are in great agreement with measured data.

Anti-inflammatory and antinociceptive activity profile of a new lead compound - LQFM219.

LQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1ß levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1ß and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.

Design, synthesis and cytotoxicity of the antitumor agent 1-azabicycles for chemoresistant glioblastoma cells.

Twelve multi-functional pyrrolizidinones, indolizidinones and pyrroliazepinones were prepared from formal aza-[3 + 2] and aza-[3 + 3] cycloadditions of five- to seven-membered heterocyclic enaminones as diverse ambident electrophiles. The antitumor activity of these alkaloid-like compounds was investigated through an initial screening performed on human glioblastoma multiform (GBM) cell lines (GL-15, U251), on murine glioma cells line (C6) and on normal glial cells. Of the compounds tested, the new pyrrolo[1,2a]azepinone, [ethyl (3-oxo-1,2-diphenyl-6,7,8,9-tetrahydro-3H-pyrrolo[1,2a]azepin-9a(5H)-yl)acetate] or (Compound-13) exhibited selective cytotoxic effects on GBM-temozolomide resistant cells. Compound-13 exerted dose-dependent cytotoxic activity by promoting arrest of cells in the G0/G1 phase of the cell cycle in the first 24 h. The apoptotic effect observed was in a time-dependent manner. Anti-migratory effect promoted by the treatment with compound-13 was also observed. Moreover, healthy mixed glial cell cultures from rat brain exhibited no cytotoxicity effect upon exposure to compound-13. Thus, the present study paves the way for the use of compound-13 as novel antitumor scaffold candidate for glioma cell therapy.

Habitat and community structure modulate fish interactions in a neotropical clearwater river

Species interactions can modulate the diversity and enhance the stability of biological communities in aquatic ecosystems. Despite previous efforts to describe fish interactions in tropical rivers, the role of habitat characteristics, community structure, and trophic traits over these interactions is still poorly understood. To investigate among-habitat variation in substratum feeding pressure and agonistic interactions between fishes, we used remote underwater videos in three habitats of a clearwater river in the Central Western, Brazil. We also performed visual surveys to estimate the abundance and biomass of fishes and proposed a trophic classification to understand how these variables can affect fish interactions. Community structure was the main factor affecting the variation in the interactions among the habitats. Biomass was the main variable determining which habitat a fish will feed on, while species abundance determined with how many other species it will interact in the agonistic interaction networks for each habitat. Specific habitats are not only occupied, but also used in distinct ways by the fish community. Overall, our results demonstrate the importance of the heterogeneity of habitats in tropical rivers for the interactions performed by the fishes and how the intensity of these interactions is affected by community structure.(AU)

Interações realizadas por peixes podem modular a diversidade e assegurar a estabilidade de comunidades em rios tropicais. Apesar dessa importância, poucos estudos relacionam as interações ecológicas com as características do habitat, estrutura da comunidade e atributos das espécies de peixes. Por meio de filmagens remotas subaquáticas nós verificamos como a pressão alimentar dos peixes sobre a comunidade bentônica e as interações agonísticas entre peixes são influenciadas por essas características do habitat e da comunidade em um rio tropical de água clara na região Centro-Oeste do Brasil. Também realizamos censos visuais para estimar a abundância e a biomassa dos peixes e propusemos uma classificação funcional para entender como essas variáveis podem afetar as interações dos peixes. A estrutura da comunidade foi o principal fator que afetou a variação nas interações entre os habitats. A biomassa dos peixes determinou em qual hábitat um peixe se alimentará, enquanto a abundância das espécies determinou com quantas outras espécies elas interagem nas redes de interações agonísticas de cada habitat. Habitats específicos não são apenas ocupados, mas também utilizados de maneiras distintas pela comunidade de peixes. Nossos resultados demonstram a importância da heterogeneidade de habitats para as interações realizadas pelos peixes em rios tropicais e como a intensidade dessas interações é afetada pela estrutura da comunidade.(AU)

The surprising "B-side": description of a new foraging tactic for the pearl cichlid, Geophagus brasiliensis, in a coastal stream of the Atlantic Forest / O surpreendente "lado-B": descrição de uma nova tática de forrageamento para o acará, Geophagus brasiliensis, em um riacho costeiro da Mata Atlântica

Abstract: A new foraging tactic for the pearl cichlid, Geophagus brasiliensis, is described from underwater observations performed in a coastal stream of the Atlantic Forest, Southeastern Brazil. Named "shift picking", the foraging tactic involved the manoeuvering of leaves, wood twigs and tree bark present in the substrate, with fish using its mouth to turn objects and uncover macroinvertebrates adhered to the underside of the object being picked ("B-side"). The object-shifting behaviour is rarely reported for fish and the present description seems to be the first record for a freshwater species of South America.

Resumo: Uma nova tática de forrageamento do acará, Geophagus brasiliensis, é descrita a partir de observações subaquáticas realizadas em um riacho costeiro da Mata Atlântica, Sudeste do Brasil. Chamada de "virar para pegar", a tática de forrageamento envolve o movimento de folhas, galhos e cascas de árvores presentes no substrato, com os peixes usando a boca para virar objetos e expor macroinvertebrados aderidos à parte de baixo dos objetos explorados ("lado B"). O comportamento de mover objetos é raramente relatado e o presente trabalho parece ser o primeiro registro para uma espécie de água doce da América do Sul.

Mixed-type femoroacetabular impingement associated with subspine impingement: recognizing the trifocal femoropelvic impingement.

To describe the arthroscopic surgical technique for subspine impingement (SSI) of the anterior inferior iliac spine (AIIS) associated with mixed type femoroacetabular impingement (FAI), through two standard arthroscopic portals (anterolateral and distal mid-anterior) in two patients with trifocal impingement. The authors report the cases of two young male patients, aged 32 and 36 years old, with trifocal femoropelvic impingement (TFPI). The technique consists of segmental capsulectomy, arthroscopic dissection of the AIIS, partial release of the direct head of the rectus femoris, resection of the AIIS projection with a burr and with fluoroscopic aid, correction of the pincer deformity, repair of the labrum with bioabsorbable anchors, and femoral osteoplasty. Details of the diagnostic workup and of the surgical technique are provided and discussed. In these cases, full range of motion was regained after surgery, as well as complete relief of pain, which was sustained in the last follow-up, one year post-operatively. Radiographs show adequate correction of the deformities in all three impingement sites. Simultaneous correction of the three sites (cam, pincer, and subspinal) provided full relief of symptoms and allowed return to work and sports. The authors propose that when approaching the symptomatic SSI, the possibility of concomitant FAI should always be considered and, in those cases, the approach must be comprehensive.

O objetivo deste trabalho foi descrever a abordagem cirúrgica artroscópica do impacto subespinhal (ISE) da espinha ilíaca anteroinferior (EIAI) associado ao impacto femoroacetabular (IFA) misto, por meio de dois portais artroscópicos padrão (anterolateral e medioanterior distal) em pacientes com impacto trifocal. Os autores relatam os casos de dois pacientes do sexo masculino, de 32 e 36 anos, com impacto femoropelvico trifocal (IFPT). A técnica consiste na ressecção segmentar da cápsula, dissecção artroscópica da EIAI com liberação parcial do reto femoral, osteoplastia com ressecção da proeminência com lâmina óssea e auxílio radioscópico, correção do pincer, reparo da lesão condrolabial com âncoras e osteoplastia femoral. Detalhes sobre o diagnóstico e a técnica são apresentados e discutidos. Nos casos operados, foi observada recuperação do arco de movimento normal do quadril e ausência de dor, que se mantiveram por um ano pós-operatório. Radiografias demonstram boa correção dos três focos de impacto em ambos os pacientes. A simultânea correção do IFPT nos seus três componentes (came, pincer e subespinhal) promoveu alívio completo dos sintomas e o retorno ao trabalho e aos esportes. Propõe-se que, na abordagem do ISE sintomático, sempre seja considerada a possibilidade da presença de IFA associado; nesses casos, a abordagem deve ser completa.

Mixed-type femoroacetabular impingement associated with subspine impingement: recognizing the trifocal femoropelvic impingement / Impacto femoroacetabular misto associado a impacto subespinhal: reconhecimento do impacto femoropelvico trifocal

ABSTRACT To describe the arthroscopic surgical technique for subspine impingement (SSI) of the anterior inferior iliac spine (AIIS) associated with mixed type femoroacetabular impingement (FAI), through two standard arthroscopic portals (anterolateral and distal mid-anterior) in two patients with trifocal impingement. The authors report the cases of two young male patients, aged 32 and 36 years old, with trifocal femoropelvic impingement (TFPI). The technique consists of segmental capsulectomy, arthroscopic dissection of the AIIS, partial release of the direct head of the rectus femoris, resection of the AIIS projection with a burr and with fluoroscopic aid, correction of the pincer deformity, repair of the labrum with bioabsorbable anchors, and femoral osteoplasty. Details of the diagnostic workup and of the surgical technique are provided and discussed. In these cases, full range of motion was regained after surgery, as well as complete relief of pain, which was sustained in the last follow-up, one year post-operatively. Radiographs show adequate correction of the deformities in all three impingement sites. Simultaneous correction of the three sites (cam, pincer, and subspinal) provided full relief of symptoms and allowed return to work and sports. The authors propose that when approaching the symptomatic SSI, the possibility of concomitant FAI should always be considered and, in those cases, the approach must be comprehensive.

RESUMO O objetivo deste trabalho foi descrever a abordagem cirúrgica artroscópica do impacto subespinhal (ISE) da espinha ilíaca anteroinferior (EIAI) associado ao impacto femoroacetabular (IFA) misto, por meio de dois portais artroscópicos padrão (anterolateral e medioanterior distal) em pacientes com impacto trifocal. Os autores relatam os casos de dois pacientes do sexo masculino, de 32 e 36 anos, com impacto femoropelvico trifocal (IFPT). A técnica consiste na ressecção segmentar da cápsula, dissecção artroscópica da EIAI com liberação parcial do reto femoral, osteoplastia com ressecção da proeminência com lâmina óssea e auxílio radioscópico, correção do pincer, reparo da lesão condrolabial com âncoras e osteoplastia femoral. Detalhes sobre o diagnóstico e a técnica são apresentados e discutidos. Nos casos operados, foi observada recuperação do arco de movimento normal do quadril e ausência de dor, que se mantiveram por um ano pós-operatório. Radiografias demonstram boa correção dos três focos de impacto em ambos os pacientes. A simultânea correção do IFPT nos seus três componentes (came, pincer e subespinhal) promoveu alívio completo dos sintomas e o retorno ao trabalho e aos esportes. Propõe-se que, na abordagem do ISE sintomático, sempre seja considerada a possibilidade da presença de IFA associado; nesses casos, a abordagem deve ser completa.

LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels.

AIMS: This study reports the biological properties of LQFM030 in vivo, a molecular simplification of the compound nutlin-1. MAIN METHODS: Ehrlich ascites tumor (EAT)-bearing mice were treated intraperitoneally with LQFM030 (50, 75 or 150mg/kg) for 10days to determine changes in ascites tumor volume, body weight, cytotoxicity and angiogenesis. Moreover, flow cytometric expression of p53 and p21 proteins and caspase-3/7, -8 and -9 activation were investigated in EAT cells from mice treated. Acute oral systemic toxicity potential of LQFM030 in mice was also investigated using an alternative method. KEY FINDINGS: Treatment of EAT-bearing mice with LQFM030 resulted in a marked decline in tumor cell proliferation and the vascular endothelial growth factor (VEGF) levels along with enhanced survival of the mice. Apoptotic tumor cell death was detected through p53 and p21 modulation and increase of caspase-3/7, -8 and -9 activity. LQFM030 also showed orally well tolerated, being classified in the UN GHS category 5 (LD50>2000-5000mg/Kg). SIGNIFICANCE: LQFM030 seems to be a promising antitumor candidate for combinatory therapy with typical cytotoxic compounds, reducing the toxicity burden while allowing a superior anticancer activity. Moreover, these data also open new perspectives for LQFM030 as an antiangiogenic agent for treatment of diseases involving VEGF overexpression.

Antinociceptive, anti-inflammatory and anxiolytic-like effects of the ethanolic extract, fractions and Hibalactone isolated from Hydrocotyle umbellata L. (Acariçoba) - Araliaceae.

Hydrocotyle umbellata Linn. (Araliaceae) is specie used in the treatment of inflammatory diseases. Crude extract (E-HU) was prepared from H. umbellata subterraneous parts and fractionated by liquid-liquid partition, resulting hexane fraction (HF-HU), dichloromethane fraction (DF-HU), ethyl acetate fraction (EAF-HU) and aqueous fraction (AF-HU). The hibalactone (HU-1) was isolated from the DF-HU and its structure was elucidated by 1H NMR and 13C NMR Spectroscopy, mass spectrometry and crystallographic x-ray analysis. The formalin-induced nociception was used to evaluate antinociceptive activity; carrageenan-induced edema and pleurisy tests to evaluate anti-inflammatory activity and light-dark box to evaluate anxiolytic-like activity in mice. The acute oral treatments with E-HU (1000mg/kg), DF-HU (150mg/kg), EAF-HU (400mg/kg) and HU-1 (33mg/kg) decreased the licking time in both phases of the formalin test. In the carrageenan-induced inflammation models, the treatment with the same doses of E-HU, DF-HU, EAF-HU and HU-1 reduced the paw edema formation and leukocytes account into pleural cavity. In silico findings suggest that hibalactone present anti-inflammatory activity by interacting with the enzymes 5-lipoxygenase and cyclooxygenase-2. In the light dark box, the treatments with DF-HU, EAF-HU and HU-1 revealed an anxiolytic like effect. Thus, the E-HU and fractions of H. umbellata showed antinociceptive, anti-inflammatory and anxiolytic like activities, as also hibalactone, a possible phytoconstituent responsible for the biological effects of this specie.

A novel chalcone derivative, LQFM064, induces breast cancer cells death via p53, p21, KIT and PDGFRA.

This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21µM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor. LQFM064) (4) (21µM) induced cell cycle arrest at G0/G1 phase with increased p53 and p21 expressions. It was also shown that the compound (4) did not interfere directly in p53/MDM2 complexation of MCF7 cells. In these cells, externalization of phosphatidylserine, cytochrome c release, increased expression of caspases-7, -8 and -9, reduced mitochondrial membrane potential and ROS overgeneration were also detected following LQFM064 (4) treatment. Further analysis revealed the activation of both apoptotic pathways via modulation of the proteins involved in the extrinsic and intrinsic pathways with an increase in TNF-R1, Fas-L and Bax levels and a reduction in Bcl-2 expression. Furthermore, KIT proto-oncogene receptor tyrosine kinase, insulin-like growth factor (IGF1) and platelet-derived growth factor receptor A (PDGFRA) were downregulated, while glutathione S-transferase P1 (GSTP1) and interferon regulatory factor 5 (IRF5) expressions were increased by LQFM064 (4)-triggered cytotoxic effects in MCF7 cells. Moreover, it can be inferred that compound (4) has a moderate acute oral systemic toxicity hazard, since its estimated LD50 was 452.50mg/kg, which classifies it as UN GHS Category 4 (300mg/kg>LD50<2000mg/kg). Furthermore, LQFM064 (4) showed a reduced potential myelotoxicity (IC50=150µM for mouse bone marrow hematopoietic progenitors). In conclusion, LQFM064 (4) was capable of inducing breast cancer cells death via different cytotoxic pathways. Thus, it is a promising alternative for the treatment of neoplasias, especially in terms of the drug resistance development.

Injuries caused by the venomous catfish pintado and cachara (Pseudoplatystoma genus) in fishermen of the Pantanal region in Brazil.

INTRODUCTION: the fishing activity throughout the Upper Paraguay River Basin has huge financial and biological importance. This retrospective study investigated the occurrence of injuries caused by fish of the Pseudoplatystoma genus (spotted catfish or pintado and striped catfish or cachara) in professional fishermen of the Pantanal of Mato Grosso do Sul State. METHODS: we collected information through a questionnaire, showing that fishing is carried out by workers with low level of education, mainly adults or seniors with low financial gains. RESULTS: in Miranda town, 126 of 315 fishermen were interviewed and 38 individuals reported injuries (30.16%). In Corumbá town, 355 of 627 fishermen were interviewed, and 111 (56,61%) reported injuries. The lacerated lesions were the most common, associate with edema, erythema, radiating pain to the root of the limb, paresthesias and local necrosis. More rarely, they reported the occurrence of fever, cardiac arrhythmias and cold sweating. These manifestations may be associated with late secondary infections or envenomations caused by the toxins in the stingers of the fish. Many questionable and inappropriate treatments are used, sometimes aggravating the injuries. CONCLUSIONS: the freshwater professional fishermen need guidance on first aid measures and prevention of accidents caused by these venomous fish.

Metal complexes of a pentadentate N2O3bis(semicarbazone) Schiff-base. A case study of structure-spectroscopy correlation.

Schiff condensation of 2,6-diformyl 4-methylphenol with semicarbazide hydrochloride in 1:2 molar ratio produces the bis(semicarbazone) ligand, herein called H3L. A comprehensive spectroscopic analysis of the compound was performed by (1)H and (13)C NMR, FTIR and electronic spectroscopies. Assignments to the UV-vis spectrum of H3L were supported by semi-empirical quantum mechanics ZINDO/S calculations. The ligand H3L forms monoclinic crystals in the space group P21/c and its structure is stabilized by classic hydrogen bonds with propanone molecules. It promptly reacts with first row metal ions to produce the following coordination compounds: [Co2(L)(µ-NO3)]·DMF, [Ni2(H2L)(µ-CH3COO)(CH3COO)2]·2H2O, [Cu2(L)(µ-NO3)(H2O)2]·H2O, [Cu2(L)(µ-CH3COO)(H2O)2]·H2O and [Cu2(H2L)(µ-Cl)Cl2]·3H2O, that have different compositions, depending on the degree of deprotonation of the ligand upon coordination. Electronic and EPR spectroscopies as well as effective magnetic moment measurements of the complexes were used in an attempt to better understand their mode of coordination, the microsymmetry around the metal ions and magnetic properties.

Taraxerol 4-Methoxybenzoate, an in vitro Inhibitor of Photosynthesis Isolated from Pavonia multiflora A. St-Hil. (Malvaceae).

A phytochemical study of Pavonia multiflora A. St-Hil. (Malvaceae) led to the isolation through chromatographic techniques of 10 secondary metabolites: vanillic acid (1), ferulic acid (2), p-hydroxybenzoic acid (3), p-coumaric acid (4), loliolide (5), vomifoliol (6), 4,5-dihydroblumenol A (7), 3-oxo-α-ionol (9), blumenol C (10), and taraxerol 4-methoxybenzoate (8), the latter being a novel metabolite. Their structures were identified by (1) H- and (13) C-NMR, using one- and two-dimensional techniques, and X-ray crystallography. In this work, we report the effect of compounds 5 and 8 on several photosynthetic activities in an attempt to search for new compounds as potential herbicide agents that affect photosynthesis. Both compounds inhibited the electron flow from H2 O to methyl viologen; therefore, they act as Hill reaction inhibitors. Using polarographic techniques and studies of the fluorescence of chlorophyll a, the interaction sites of these compounds were located at photosystem II.

Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues.

Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA-4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on ß-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a-r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of ß-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values ≤18 µM and ≥4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.

Impact of ecotourism on the fish fauna of Bonito region (Mato Grosso do Sul State, Brazil): ecological, behavioural and physiological measures

Bonito, in Mato Grosso do Sul State, is an important destination for ecotourism in Brazil and the main challenge of sustainable ecotourism here has been to accommodate and adjust the increase of tourism without compromising the ecological integrity of the local ecosystems. In this study we aimed to assess the environmental impact of ecotourism on the fish fauna of Sucuri River in Bonito by integrating ecological, behaviour and physiological criteria and using the fish species Crenicichla lepidota and Moenkhausia bonita as indicators. Two distinct sites were defined to collect data: (1) affected daily by ecotourism (Tourism) and (2) undisturbed (No Tourism). The "stationary point count" method was performed to assess variations in ecological parameters and "ad libitum" and focal animal methods were used to collect behaviour data. The cortisol response of M. bonita to a stress protocol was measured from holding-water. Results showed a significantly increase in species richness, density and diversity at the Tourism site. Nevertheless, behaviour patterns indicated a higher stress at the Tourism site for both species as well higher cortisol levels for M. bonita. In opposition to the ecological measures, the behaviour and physiological ones may be interpreted as an early sign of negative impact caused by ecotourism, prior to changes at community level. Bonito, no estado de Mato Grosso do Sul, é atualmente um importante destino de ecoturismo no Brasil e o seu principal desafio tem sido o de acomodar e ajustar de forma sustentável a crescente procura de turistas sem comprometer a sua integridade ecológica. O objetivo deste estudo consistiu em avaliar o impacto do ecoturismo na ictiofauna do rio Sucuri localizado em Bonito, através da utilização integrada de critérios ecológicos, comportamentais e fisiológicos e utilizando as espécies de peixes Crenicichla lepidota e Moenkhausia bonita como indicadores. Para tal foram determinadas duas áreas distintas de amostragens no rio: (1) local onde ocorrem visitas turísticas diárias (Tourism) e (2) local sem qualquer tipo de impacto humano (No Tourism). O método de censos visuais por pontos fixos foi utilizado para determinar variações nos parâmetros ecológicos e os métodos "ad libitum" e animal focal foram utilizados para coletar dados comportamentais para as duas espécies em estudo. A resposta fisiológica à presença de turistas foi testada em M. bonita através da determinação de cortisol na água por um método não-invasivo de captura, transporte e confinamento. Os resultados obtidos indicam que no local exposto ao turismo há um aumento significativo da riqueza específica, densidade e diversidade de espécies. No entanto, a nível comportamental C. lepidota apresenta mudanças significativas de comportamento alimentar, agonístico, de fuga e guarda do ninho entre os dois locais. Moenkhausia bonita apresenta mudanças significativas não só a nível do seu comportamento alimentar e de fuga, mas também apresenta níveis de cortisol significativamente superiores no local com turismo. Contrariamente aos dados ecológicos, os resultados comportamentais e fisiológicos poderão ser interpretados numa primeira análise como impactos negativos do ecoturismo que surgem em antecipação a mudanças significativas na estrutura e composição das comunidades.