Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).

Virtual Screening of Natural Products Database.

Constant research on natural products has generated, over time, a large number of compounds with the potential to be evaluated in several biological tests and subsequently have been cataloged in databases that allow other researchers to perform virtual screenings of activity in various biological systems. This considerably reduces the time for the development of new drugs. This review describes the main databases of natural products available for searching bioactive compounds. It also describes the main features of virtual screening strategies for the identification of molecules with the potential to be used as new drugs. In addition, a search was made in the Web of Science database, using the search term "Virtual screening of natural products databases" from 2003 to 2018. The search criterion resulted in 230 articles, which had their abstracts evaluated with pertinence to the criteria required for this work, which are: a) be a research article; b) performing a virtual screening on databases of natural products or containing natural products; and c) works that identified drug candidate molecules. Based on these criteria, the bibliographic review on the topic was excluded. After this analysis, 104 works were selected for this review. We selected relevant papers describing the potential drug candidates that were distributed in 15 classes, of which the anticancer, antibacterial and anti-inflammatory hits were the most abundant. The works showing efforts to search for new molecules against various other diseases in distinct biological systems were also described. In this way, this work shows an overview of several methodologies and we hope they can help and inspire the development of new research to improve people's quality of life.

Virtual screening and assessment of anticancer potential of selenium-based compounds against HL-60 and MCF7 cells.

Aim: Selenium-based compounds have antitumor potential. We used a ligand-based virtual screening analysis to identify selenoglycolicamides with potential antitumor activity. Results & Conclusion: Compounds 3, 6, 7 and 8 were selected for in vitro cytotoxicity tests against various cell lines, according to spectrophotometry results. Compound 3 presented the best cytotoxicity results against a promyelocytic leukemia line (HL-60) and was able to induce cell death at a frequency similar to that observed for doxorubicin. The docking study showed that compound 3 has good interaction energies with the targets caspase-3, 7 and 8, which are components of the apoptotic pathway. These results suggested that selenium has significant pharmacological potential for the selective targeting of tumor cells, inducing molecular and cellular events that culminate in tumor cell death.

In Silico Studies for Bacterystic Evaluation against Staphylococcus aureus of 2-Naphthoic Acid Analogues.

BACKGROUND: Staphylococcus aureus is a gram-positive spherical bacterium commonly present in nasal fossae and in the skin of healthy people; however, in high quantities, it can lead to complications that compromise health. The pathologies involved include simple infections, such as folliculitis, acne, and delay in the process of wound healing, as well as serious infections in the CNS, meninges, lung, heart, and other areas. AIM: This research aims to propose a series of molecules derived from 2-naphthoic acid as a bioactive in the fight against S. aureus bacteria through in silico studies using molecular modeling tools. METHODS: A virtual screening of analogues was done in consideration of the results that showed activity according to the prediction model performed in the KNIME Analytics Platform 3.6, violations of the Lipinski rule, absorption rate, cytotoxicity risks, energy of binder-receptor interaction through molecular docking, and the stability of the best profile ligands in the active site of the proteins used (PDB ID 4DXD and 4WVG). RESULTS: Seven of the 48 analogues analyzed showed promising results for bactericidal action against S. aureus. CONCLUSION: It is possible to conclude that ten of the 48 compounds derived from 2-naphthoic acid presented activity based on the prediction model generated, of which seven presented no toxicity and up to one violation to the Lipinski rule.

Larvicidal Compounds Extracted from Helicteres velutina K. Schum (Sterculiaceae) Evaluated against Aedes aegypti L.

Helicteres velutina K. Schum (Sterculiaceae), a member of Malvaceae sensu lato, is a Brazilian endemic plant that has been used by the indigenous tribe Pankarare as an insect repellent. A previous study has reported the isolation of terpenoids, flavonoids and pheophytins, in addition to the larvicidal activity of crude H. velutina extracts derived from the aerial components (leaves, branches/twigs, and flowers). The present study reports the biomonitoring of the effects of fractions and isolated compounds derived from H. velutina against A. aegypti fourth instar larvae. A crude ethanol extract was submitted to liquid-liquid extraction with hexane, dichloromethane, ethyl acetate and n-butanol to obtain their respective fractions. Larvicidal evaluations of the fractions were performed, and the hexane and dichloromethane fractions exhibited greater activities than the other fractions, with LC50 (50% lethal concentration) values of 3.88 and 5.80 mg/mL, respectively. The phytochemical study of these fractions resulted in the isolation and identification of 17 compounds. The molecules were subjected to a virtual screening protocol, and five molecules presented potential larvicidal activity after analyses of their applicability domains. When molecular docking was analysed, only three of these compounds showed an ability to bind with sterol carrier protein-2 (1PZ4), a protein found in the larval intestine. The compounds tiliroside and 7,4'-di-O-methyl-8-O-sulphate flavone showed in vitro larvicidal activity, with LC50 values of 0.275 mg/mL after 72 h and 0.182 mg/mL after 24 h of exposure, respectively. This is the first study to demonstrate the larvicidal activity of sulphated flavonoids against A. aegypti. Our results showed that the presence of the OSO3H group attached to C-8 of the flavonoid was crucial to the larvicidal activity. This research supports the traditional use of H. velutina as an alternative insecticide for the control of A. aegypti, which is a vector for severe arboviruses, such as dengue and chikungunya.

Virtual screening of secondary metabolites of the genus Solanum with potential antimicrobial activity

ABSTRACT Infectious diseases are a health problem today and have high mortality rates with a wide diversity of potentially pathogenic microorganisms. Research that is based either on the search for new drugs from plants or on the improvement of phytotherapeutics is prominent and continues to play an important role nowadays. From this perspective, use of in silico studies to carry out investigations of new molecules potentially active for methicillin-resistant Staphylococcus aureus and Escherichia coli using an in-house database with 421 different secondary metabolites selected from the literature from Solanum genus was performed. We also realized an in vitro study with strains of S. aureus and E. coli and compared the results. Two databases from ChEMBL were selected, the first one with activity against methicillin-resistant S. aureus and another against E. coli. The compounds were classified according to the pIC50 values to generate and validate the model using a "Random Forest". The "Random Forest" prediction model for methicillin-resistant S. aureus obtained an accuracy of 81%, area under the Receiver Operating Characteristic curve of 0.885, selecting eight molecules with an active potential above 60%. The prediction model for E. coli obtained an accuracy rate of 88%, area under the Receiver Operating Characteristic curve of 0.932, selecting four molecules with potential probability above 84%. Rutin proved to be potentially active in the in silico study for S. aureus and E. coli. Microbiological tests have shown that rutin has activity only for E. coli. An interaction study with strains of S. aureus ATCC 25923, a standard strain sensitive to all antibiotics, and SAM-01, a multidrug-resistant strain, was designed. There was interaction only between rutin and oxacillin, one of the three antibiotics studied in the interaction, for the strain SAM-01, reducing the resistance of this strain.

Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control.

As recently described, adherence to the Mediterranean diet is associated with improved asthma control. However, evidence of how specific nutrients such as fatty acids and antioxidants may affect this relationship remains largely unknown. We aimed to examine the association between dietary intake of fatty acids and antioxidants and asthma control. A cross-sectional study was developed in 174 asthmatics, mean age of 40 (SD 15) years. Dietary intake was obtained by a FFQ, and nutritional content was calculated using Food Processor Plus™ software (ESHA Research, Inc., Salem, OR, USA). Good asthma control was defined by the combination of forced expiratory volume during the first second, exhaled NO (eNO) and Asthma Control Questionnaire (ACQ) score (control: forced expiratory volume in the first second ≥80 %; eNO ≤35 ppb; ACQ <1·0, scale 0-6 score). Multiple linear and logistic regression models were performed to analyse the associations between nutrients and asthma outcomes, adjusting for confounders. A high n-6:n-3 PUFA ratio predicted high eNO, whereas high intakes of n-3 PUFA, a-linolenic acid (ALA) and SFA were associated with low eNO. Odds for controlled asthma improved along with an increased intake of n-3 PUFA (OR 0·14, 95% CI 0·04, 0·45; P for trend=0·001), SFA (OR 0·36, 95% CI 0·13, 0·97; P for trend=0·047) and ALA (OR 0·18, 95% CI 0·06, 0·58; P for trend=0·005). A high n-6:n-3 PUFA ratio increased the odds for uncontrolled asthma (OR 3·69, 95% CI 1·37, 9·94; P for trend=0·009), after adjusting for energy intake, sex, age, education and use of inhaled corticosteroids. Higher intakes of n-3 PUFA, ALA and SFA were associated with good asthma control, while the risk for uncontrolled asthma increased with a higher n-6:n-3 PUFA ratio. The present results introduce a protective effect of ALA in asthma control, independent of marine n-3 fatty acids, and provide a rationale to dietary intervention studies in asthma.

[In vitro insecticidal activity of seed neem oil on Lutzomyia longipalpis (Diptera: Psychodidae)]. / Atividade inseticida in vitro do óleo de sementes de nim sobre Lutzomyia longipalpis (Diptera: Psychodidae).

Lutzomyia longipalpis is the main vector of visceral leishmaniasis in Brazil. The objective was to evaluate the effect of oil from (Azadirachta indica) neem seeds on eggs, larvae and adults of the vector. The insects were captured in the field and kept in the laboratory at +/- 27 °C and 80% relative humidity. Five treatments with different concentrations were performed using two negative controls (distilled water and Tween 80) and a positive control. The eggs were sprayed with the oil at different concentrations and the number of hatched larvae evaluated for 10 days. Mortality of larvae was observed to pupation and adult mortality was observed after 24, 48, and 72 hours. Statistical analysis was performed by Tukey test at 5% probability. The highest oil concentration of eggs obtained 65.16 +/- 3.24% efficacy for reducing egg hatching. The test with larvae showed 67.75 +/- 2.21% efficacy at a concentration of 100 mg.mL⁻¹. In adults, the efficacy of the 100 mg.mL⁻¹ concentration was 96.64 +/- 4.11% after 24 hours. The phytochemical analysis revealed the presence of triterpenes. These results demonstrate the potential use of this oil in the control of this vector.

Atividade inseticida in vitro do óleo de sementes de nim sobre Lutzomyia longipalpis (Diptera: Psychodidae) / In vitro insecticidal activity of seed neem oil on Lutzomyia longipalpis (Diptera: Psychodidae)

Lutzomyia longipalpis é o principal vetor da Leishmaniose visceral no Brasil. O objetivo deste trabalho foi avaliar o efeito do óleo de sementes de nim (Azadirachta indica) sobre ovos, larvas e adultos do vetor. Os insetos foram capturados no campo e mantidos no laboratório a ± 27 °C e 80 por cento de umidade relativa. Cinco tratamentos com diferentes concentrações foram realizados, usando-se dois controles negativos, um com água destilada e outro com Tween 80 (3 por cento) e um controle positivo com cipermetrina. Os ovos foram borrifados com o óleo em diferentes concentrações e avaliou-se o número de larvas eclodidas por 10 dias consecutivos. A mortalidade das larvas foi observada até a pupação, e a mortalidade dos adultos foi observada após 24, 48, e 72 horas. A análise estatística foi feita pelo teste de Tukey a 5 por cento de probabilidade. No teste com ovos, a maior concentração obteve 65,16 ± 3,24 por cento de eficácia. O teste com larvas apresentou 67,75 ± 2,21 por cento de eficácia na concentração de 100 mg.mL-1. Com adultos, a eficácia na concentração de 100 mg.mL-1 foi de 96,64 ± 4,11 por cento, após 24 horas. A análise fitoquímica revelou a presença de triterpenos. Esses resultados demonstram o potencial uso desse óleo no controle deste vetor.

Lutzomyia longipalpis is the main vector of visceral leishmaniasis in Brazil. The objective was to evaluate the effect of oil from (Azadirachta indica) neem seeds on eggs, larvae and adults of the vector. The insects were captured in the field and kept in the laboratory at ± 27 °C and 80 percent relative humidity. Five treatments with different concentrations were performed using two negative controls (distilled water and Tween 80) and a positive control. The eggs were sprayed with the oil at different concentrations and the number of hatched larvae evaluated for 10 days. Mortality of larvae was observed to pupation and adult mortality was observed after 24, 48, and 72 hours. Statistical analysis was performed by Tukey test at 5 percent probability. The highest oil concentration of eggs obtained 65.16 ± 3.24 percent efficacy for reducing egg hatching. The test with larvae showed 67.75 ± 2.21 percent efficacy at a concentration of 100 mg.mL-1. In adults, the efficacy of the 100 mg.mL-1 concentration was 96.64 ± 4.11 percent after 24 hours. The phytochemical analysis revealed the presence of triterpenes. These results demonstrate the potential use of this oil in the control of this vector.

Atividade ovicida e larvicida in vitro do óleo essencial de Eucalyptus globulus sobre Haemonchus contortus / Ovicidal and larvicidal activity in vitro of Eucalyptus globulus essential oils on Haemonchus contortus

O objetivo deste trabalho foi avaliar o efeito do óleo essencial de Eucalyptus globulus (OEEG) sobre a eclosão e desenvolvimento de larvas de Haemonchus contortus. A determinação da composição química do OEEG foi feita por meio de cromatografia gasosa acoplada à espectrometria de massa. No teste de eclosão de ovos (TEO), utilizaram-se as concentrações 21,75; 17,4; 8,7; 5,43 e 2,71 mg.mL-1; e no de desenvolvimento larvar (TDL) as concentrações foram 43,5; 21,75; 10,87; 5,43 e 2,71 mg.mL-1. Cada ensaio foi acompanhado por um controle positivo, 0,02 mg.mL-1 tiabendazol, no TEO e 0,008 mg.mL-1 ivermectina no TDL, e por um controle negativo com o diluente Tween 80 (3 por cento). A eficácia máxima obtida pelo OEEG sobre ovos foi de 99,3 por cento na concentração de 21,75 mg.mL-1 e, sobre larvas, 98,7 por cento na concentração de 43,5 mg.mL-1. A concentração do OEEG, que inviabilizou 50 por cento dos ovos e das larvas do parasito, foi de 8,3 e 6,92 mg.mL-1, respectivamente. A análise química do óleo identificou como principal componente o monoterpeno 1,8-cineol. O OEEG apresentou atividade ovicida e larvicida in vitro sobre H. contortus, determinando um bom potencial para utilização no controle de nematóides gastrintestinais de ovinos e caprinos.

The objective of this work was to evaluate ovicidal and larvicidal effects of Eucalyptus globulus essential oil (EGEO) on Haemonchus contortus. The chemical composition determination of EGEO was through gas chromatography and mass spectrometry. Egg hatch test (EHT) was performed in concentrations 21.75; 17.4; 8.7; 5.43 e 2.71 mg.mL-1. In larval development test (LDT) were used the concentrations 43.5; 21.75; 10.87; 5.43 e 2.71 mg.mL-1. Each trial was conducted by negative control with Tween 80 (3 percent) and positive control, 0.02 mg.mL -1 of thiabendazole in EHT and 0.008 mg.mL-1 of ivermectin in LDT. The maximum effectiveness of EGEO on eggs was 99.3 percent in concentration of 21.75 mg.mL-1 and on larvae was 98.7 percent in concentration 43.5 mg.mL-1. The concentration of EGEO that inhibits 50 percent of the eggs and larvae was 8.3 and 6.92 mg.mL-1, respectively. The oil chemical analysis identified as main component the monoterpen 1,8-cineol. EGEO presented ovicidal and larvicidal activities in vitro, revealing a good potential for use in the control of sheep and goat gastrointestinal nematodes.