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Antarctica has a great diversity of microorganisms with biotechnological potential but is not very well Known about yeasts with phosphate solubilization activity. Thus, the aim of this study was to evaluate the ability of yeasts from Antarctica lichens to solubilize phosphate in vitro. In the screening, 147 yeasts were tested and 43 (29%) showed P solubilization in solid NBRIP medium at 15.0 °C, with a higher prevalence of positive genera Vishniacozyma, followed by Cystobasidium. Most of the positive yeasts were isolated from Usnea auratiacoatra, followed by Polycauliona regalis and Lecania brialmontii. Two strains with better activity after screening were selected for the solubilization in the liquid medium, Vishniacozyma victoriae 2.L15 and A.L6 (unidentified). Vishniacozyma victoriae 2.L15 exhibiting activities at 25.0 °C (29.91 mg/L of phosphate and pH 6.85) and at 30.0 °C (619.04 mg/L of phosphate and pH 3.73) and A.L6 strain at 25.0 °C (25.05 mg/L of phosphate and pH 6.69) and at 30.0 °C (31.25 mg/L of phosphate and pH 6.47). Of eight organic acids tested by HPLC, tartaric and acetic acids were detected during phosphate solubilization, with greater release in the period of 144 (2.13 mg/L) and 72 (13.72 mg/L) hours, respectively. Future studies to elucidate the presence of functional genes for P metabolism in lichens, as well as studies in the field of proteomics for the discovery of yeast proteins related to P solubilization are needed. Thus, the high prevalence of lichen-associated yeast communities probably contributed to the high frequency of phosphate-solubilizing isolates in this study.

Background The cashew stem borer Anthistarcha binocularis (Meyrick) is a major pest in cashew orchards in Brazil. The damage caused by the larvae results in economic losses, and the available chemical control is not suitable because of the endophytic nature of A. binocularis. The identification of the A. binocularis sex pheromone could provide novel applications for the detection and monitoring of this species. Results Two compounds from female sex gland extracts elicited electrophysiological responses on male antennae. They were identified as dodec-6-en-1-ol and dodec-6-en-1-yl acetate by gas chromatography-mass spectrometry. E/Z stereoisomers of both compounds were synthesized, and the electroantennograms for the synthetic compounds showed the strongest responses for the (E)-stereoisomers of the alcohol and acetate. In a field trial, the E6-12:OH/E6-12:OAc mixture attracted male A. binocularis, whereas the Z6-12:OH/Z6-12:OAc mixture attracted no specimens. Conclusions The bioactive compounds from the sex pheromone of A. binocularis have been identified as a mixture of two previously unidentified pheromone compounds: E6-12:OH and E6-12:OAc. The mixture of both compounds was attractive to males in preliminary field experiments, and this study is the first report of Δ6-unsaturated monoenyl pheromone compounds in Lepidoptera. © 2019 Society of Chemical Industry.

Background: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. Objective: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds. Method: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. Result: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. Conclusion: The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

In association with lichens, bacteria can play key roles in solubilizing sources of inorganic phosphates that are available in the environment. In this study, the potential of bacteria isolated from 15 Antarctic lichen samples for phosphate solubilization was investigated. From 124 bacteria tested, 66 (53%) were positive for phosphate solubilization in solid NBRIP medium, with a higher prevalence of Pseudomonas, followed by Caballeronia and Chryseobacterium. Most of the phosphate-solubilizing bacteria were isolated from Usnea auratiacoatra, followed by Caloplaca regalis and Xanthoria candelaria. Two isolates showed outstanding performance, Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, since they presented solubilization in the temperature range from 15.0 to 30.0 °C, and maximum quantification of soluble phosphate at 25.0 °C was 511.21 and 532.07 mg/L for Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, respectively. At 30.0 °C soluble phosphate yield was 639.43 and 518.95 mg/L with pH of 3.74 and 3.87 for Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, respectively. Fumaric and tartaric acids were released during the solubilization process. Finally, bacteria isolated from Antarctic lichens were shown to have the potential for phosphate solubilization, opening perspectives for future application in the agricultural sector and contributing to reduce the use of chemical fertilizers.

The giant sugarcane borer Telchin licus (Drury, 1773) (Lepidoptera: Castniidae) is a day-flying moth pest of sugarcane, pineapples and bananas. To better understand the chemical communication in this species, we examined the morphology of its olfactory system and the chemical composition of its body parts. The ventral surface of the clubbed antennae of T. licus has six morphological types of sensilla: sensilla trichodea, basiconica, chaetica, squamiforma, coeloconica, and auricillica. The telescopic ovipositor shows no evidence of a sexual gland, or female-specific compounds. On the other hand, the midleg basitarsus of males releases (E,Z)-2,13-octadecadienol and (Z,E)-2,13-octadecadienol, which are electroantennographically active in both sexes. These compounds are known female sex pheromones in the Sesiidae family and are male-specific compounds in another castniid moth, although further investigations are necessary to elucidate their ecological role in the Castniidae family.

Background Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine. Methods Mice were treated with LQM01 (5, 10, 25 or 50 mg/kg, i.p.), vehicle (0.9% saline i.p.) or a standard drug. The mice were subjected to carrageenan-induced pleurisy, abdominal writhing induced by acetic acid, the formalin test and the hot-plate test. The model of non-inflammatory chronic muscle pain induced by saline acid was also used. Mice from the chronic protocol were assessed for withdrawal threshold, muscle strength and motor coordination. LQM01 or vehicle treated mice were evaluated for Fos protein. Results LQM01 inhibits TNF-α and IL-1β production, as well as leukocyte recruitment during inflammation process. The level of IL-10 in LQM01-treated mice increased in pleural fluid. In addition, LQM01 decreased the nociceptive behavior in the acetic acid induced writhing test, the formalin test (both phases) and increased latency time on the hot-plate. LQM01 treatment also decreased mechanical hyperalgesia in mice with chronic muscle pain, with no changes in muscle strength and motor coordination. LQM01 reduced the number of Fos positive cells in the superficial dorsal horn. This compound exhibited antioxidant properties in in vitro assays. Conclusions LQM01 has an outstanding anti-inflammatory and analgesic profile, probably mediated through a reduction in proinflammatory cytokines release, increase in IL-10 production and reduction in neuron activity in the dorsal horn of the spinal cord in mice. General significance Beneficial effects of LQM01 suggest that it has some important clinical features and can play a role in the management of ‘dysfunctional pain’ and inflammatory diseases.

The sugarcane hairy borer, Hyponeuma taltula (Schaus, 1904), attacks the base of sugarcane and causes the death of the apical bud, a symptom known as "dead heart." In recent years, there has been significant infestation in Brazilian sugarcane crops. With the purpose of finding methods for controlling and/or monitoring the pest for the sustainable cultivation of sugarcane, we characterized the mating behavior of H. taltula and confirmed the release of a sex pheromone by this insect. Sexual activity was observed between the second and ninth hour of scotophase, during which female calling caused the onset of male courtship behaviors and increased their frequency. An ethogram was built showing that males perform seven observable steps: (1) wing flapping, (2) walking with wing flapping, (3) flying, (4) flying towards the female, (5) landing near the female and walking around her, (6) attempting copulation, and (7) copulation (mating). Female sex gland extracts also triggered attraction and male courtship behaviors. These results thus confirm that the female abdominal gland produces a sex pheromone and that the presence of this pheromone in the air is needed to initiate the male courtship sequence. The sexual behavior of H. taltula is compatible with control and/or monitoring methods using female sex pheromones.

2-[(3,5-di-tert-butyl-4-hydroxyphenyl)methylene]-hydrazinecarboximidamide (WE010), 2-([1,1′-biphenyl]-4-ylmethylene)-hydrazinecarboximidamide (WE014), and 2-[(3,4-dichlorophenyl)methylene]-hydrazinecarboximidamide (WE017) are guanylhydrazone derivatives widely studied biologically and chemically; however, there are no studies regarding their thermal behaviors. The present study aims to apply the thermal analyses: differential scanning calorimetry (DSC), differential scanning calorimetry coupled to the photovisual system (DSC-photovisual), and thermogravimetry (TG), to characterize the guanylhydrazones, as well as HPLC and FTIR. The DSC curve of WE010 shows a melting process with Tonset at 190 °C and peak at 193.5 °C (∆H 41.0 J g−1). Due to the symmetry of the melting peaks obtained by DSC, it is possible to calculate the purity of the sample (98.87 %). The DSC curve of WE014 shows the melting process in the range of 208–213 °C, with a melting peak at 211 °C (∆H 61 J g−1). The DSC curve of WE017 showed Tonset at 215 °C and peak temperature of 219 °C (∆H 55 J g−1). The TG curve of WE010, WE014, and WE017 presents initial decomposition temperatures of 186.95, 197.31, and 195.44 °C, respectively. The DSC-photovisual confirmed the results of DSC and TG. The HPLC determined the purities of the samples and confirmed the results of DSC. The FTIR confirmed the thermal data. Thus, the use of thermal analysis is an important tool for the characterization of molecules with therapeutic potential contributing to the characterization and evaluation of their stability as well as nonthermal technique with complementary tool.

Background: Chagas' disease is one of the main causes of heart failure in developing countries. The disadvantages of current therapy include the undesirable side-effects, resistance, and therapeutic adhesion. The development of new efficient and safe drugs is, therefore, an issue of extreme importance. Objectives: In order to gain a better understanding of how the compounds interact with the target, computational methods are essential. Method: In this theoretical study, we report a docking protocol applied to a dataset of 173 cruzain inhibitors with IC50 values of less than 10 μM, belonging 16 different chemical classes. A preliminary analysis was performed, where the best protein structure for the study was identified. Results: The enzyme was validated by redocking and a fingerprint graph for the ligand-enzyme interactions was generated, allowing the identification of the main amino acid residues related to the activity. Additionally, a larger cluster was generated, allowing the visualization of the orientation of the compounds and providing binding information for the different classes of compounds as well as their interaction in the cruzain active site. Amino acid residues other than those known as the catalytic triad (Gly23, Cys25, and Gly65) were identified, for example, Gln19 and Asp158. Conclusion: This provides a better insight into the mode of interaction of various cruzain inhibitors, which show IC50 values in the nanomolar range but which do not interact with the triad. These findings can help researchers to find new cruzain inhibitors for use in the fight against the Chagas disease.

In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03 μM. The 8c derivative showed the highest potency against cruzain (IC50 = 2.4 μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb = −7.39 kcal·mol−1) indicates interaction (via dipole–dipole) between the hybridized sulfur sp3 atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.

Background Alzheimer`s disease (AD) affects mainly elderly people over 60 years of age. Currently, there are more than 35 million people with this disease worldwide. The enzyme β-secretase is involved in the processing of the amyloid precursor protein and plays a key role in the physiopathology of AD. The action of some acetylcholinesterase inhibitors (AChEI) as β-secretase inhibitors has been reported. Objective The aim of this study was to highlight the modes of the binding of acetylcholinesterase ligands onto the active site of the β-secretase enzyme. Methods Molecular dynamics and docking were used in order to identify pivotal interactions that favor the inhibitory activity and provide a rational basis for planning novel β-secretase inhibitors. Additionally, density functional theory (DFT) was used to provide accurate energy values for the complexes. A mechanistic study of the amide hydrolysis was also performed at the M06/6-31G(d) basis set. Results Of the 100 AChE inhibitors, 10 were able to interact with Asp32 and/or Asp228 residues from the enzyme BACE-1, suggesting that these could act as multi-target compounds. These inhibitors were selected for DFT studies in order to provide more accurate energy values. Interestingly, the range of energy values (-27.01 to -8.64 kJ mol-1) obtained was in agreement with the anti-AChE activity. The results obtained in the mechanistic study of compound 93 using DFT are in agreement with theoretical studies described in the literature. Conclusion The results reported in this study will advance our understanding of the influence of the distinct chemical structures of inhibitors at the active site and aid the development of new virtual screening protocols to design novel AChE multi-target inhibitors.

Indole alkaloids comprise a large and complex class of natural products found in a variety of marine sources. Infectious diseases remain a major threat to public health, and in the absence of long-term protective vaccines, the control of these infectious diseases is based on a small number of chemotherapeutic agents. Furthermore, the emerging resistance against these drugs makes it urgently necessary to discover and develop new, safe and, effective anti-infective agents. In this regard, the aim of this review is to highlight indole alkaloids from marine sources which have been shown to demonstrate activity against infectious diseases.

Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple fruits, popularly known as "jambolão" or "jambolan". In folk medicine, this plant is used for the treatment of diabetes and inflammatory conditions.We investigated the antinociceptive effect of ethanol extract (EE) from S. cumini leaves on orofacial nociception.The antinociceptive effects of the EE obtained from the leaves of S. cumini were evaluated in mice using formalin- and glutamate-induced orofacial nociception.ESI-MS/MS analyses demonstrated that major constituents in the analyzed samples coincided with the mass of the phenolic acids and flavonoids. In pharmacological approach, pre-treatment with EE (100, 200, or 400 mg/kg, p.o.) significantly reduced (p0.05 or p0.01) the percentage of paw licks time during phase 2 (43.2, 47.1, and 57.4%, respectively) of a formalin pain test when compared to control group animals. This effect was prevented by pretreatment with glibenclamide and N(G)-nitro-l-arginine (l-NOARG). The extract, all doses, also caused a marked inhibition (p0.01 or p0.001) of glutamate-induced orofacial nociception (38.8, 51.7, and 54.7%) when compared with the control group. No effect was observed with the rota-rod model.We can suggest that the antinociceptive effect of the EE is mediated by peripheral mechanisms, possibly involving KATP channels and the nitric oxide pathways. These effects appear to be related to the presence of flavonoids compounds, such as quercetin.

Synthesis and pharmacological evaluation of guanidinederivatives with potential hypoglycemic activity Patricia de Albuquerque Sarmento, Polliane Maria Cavalcante-Araujo, Igor Santana de Melo, Paulo Henrique Barcellos Franca, Navylla Candeia de Medeiros, Tales Lyra de Oliveira, Thais Honorio Lins, Regina Celia Sales Santos Verissimo, Maria Lysete de Assis Bastos, Eurica Adelia Nogueira Ribeiro, Robinson Sabino-Silva, Joao Xavier de Araujo-Junior