Resumo Abstract: Oil-resin from Copaifera is considered one of the most important natural product for natives of the Amazon Region due to its diverse pharmacological properties. The aim of this work was to perform the chemical characterization, the isolation of the constituents and to assess antibacterial activity focusing on diterpenic acids of the C. reticulata oil-resin. Regarding antibacterial activity, food-borne bacteria were evaluated, with the most significant activity observed for diterpenes acids against grampositive bacteria.

Raman and SERS spectroscopies have been used to identify the bioactive compounds pereirine and flavopereirine from stem bark, ethanolic crude extracts and infusions.

BACKGROUND:Chagas disease, also known as American trypanosomiasis, is classified as one of the 17 most important neglected diseases by the World Health Organization. The only drugs with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search for new effective chemical entities is a challenge to research groups and the pharmaceutical industry.OBJECTIVE:Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones and semicarbazones containing 1,2,3-1H triazole isatin scaffold.METHOD:5'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride, respectively, in methanol, using conventional reflux or microwave heating. The compounds were assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic intermediates were also evaluated for comparison.RESULTS:A series of compounds were prepared in good yields. Among the 37 compounds evaluated, 18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated alkyl chain (IC50 = 24.1, 38.6, and 83.2 µM; SI = 11.6, 11.8, and 14.0, respectively). To further elucidate the mechanism of action of these new compounds, the redox behaviour of some active and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase C (TcrPDEC).CONCLUSION:A class of thio/semicarbazones structurally simple and easily accessible was synthesized. Compounds containing thiosemicarbazone moieties showed the best results in the series, being more active than the corresponding semicarbazones. Our results indicated that the activity of these compounds does not originate from an oxidation-reduction pathway but probably from the interactions with trypanosomal enzymes.

Pyrrolizidine alkaloids are natural molecules playing important roles in different biochemical processes in nature and in humans. In this work, the electron ionization mass spectrum of retronecine, an alkaloid molecule found in plants, was investigated computationally. Its mass spectrum can be characterized by three main fragment ions having the following m/z ratios: 111, 94, and 80. In order to rationalize the mass spectrum, minima and transition state geometries were computed using density functional theory. It was showed that the dissociation process includes an aromatization of the originally five-membered ring of retronecine converted into a six-membered ring compound. A fragmentation pathway mechanism involving dissociation activation barriers that are easily overcome by the initial ionization energy was found. From the computed quantum chemical geometric, atomic charges, and energetic parameters, the abundance of each ion in the mass spectrum of retronecine was discussed.

Biodiesel demand is increasing all over the world and the inhibition of microbial growth during the storage of this biofuel is extremely important. There are few studies involving the evaluation of biocides specifically for biodiesel. In the present work, we synthesized and evaluated a set of biocide candidates from chemical transformations in triacylglycerides. Samples of pure biodiesel with the products were evaluated against microorganisms which have been isolated from biodiesel/diesel blends (fungi A. niger, A. fumigatus, C. albicans and S. cerevisiae; and bacteria B. subtilis and Acinetobacter sp.). None of the products inhibited the growth of bacteria. Four nitrated derivatives presented fungicidal activity. The nitrated derivatives were also evaluated as cetane number improvers for B7 biodiesel/diesel blend. The nitrates of soybean methoxylated ethylene glycol esters increased the cetane number by more than three points. Despite showing modest biocide activity, the results can guide the planning of new products from triacylglycerides.

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. In this work, we synthesized two series of new acylhydrazides and evaluated their activity against different strains of Mtb. Derivatives of isoniazid (INH) showed important anti-Mtb activity, some being more potent than all anti-TB drugs of first choice. Moreover, three compounds proved to be more potent than INH against resistant Mtb. The Ames test showed favorable results for two of these substances compared to INH, one of which presented expressly lower toxicity to HepG2 cells than that of INH. This result shows that this compound has the potential to overcome one of the main adverse effects of this drug.

Glioblastoma multiform (GBM) is the most common and devastating type of primary brain tumor, being considered the deadliest of human cancers. In this context, extensive efforts have been undertaken to develop new drugs that exhibit both antiproliferation and antimetastasis effects on GBM. 1,4-Naphthoquinone (1,4-NQ) scaffold has been found in compounds able to inhibit important biological targets associated with cancer, which includes DNA topoisomerase, Hsp90 and monoamine oxidase. Among potential antineoplastic 1,4-NQs is the plant-derived lapachol (2-hydroxy-3-prenyl-1,4-naphthoquinone) that was found to be active against the Walker-256 carcinoma and Yoshida sarcoma. In the present study, we examined the effect of polyamine (PA)-conjugated derivatives of lapachol, nor-lapachol and lawsone on the growth and invasion of the human GBM cells. The conjugation with PA (a spermidine analog) resulted in dose-dependent and time-dependent increase of cytotoxicity of the 1,4-NQs. In addition, in-vitro inhibition of GBM cell invasion by lapachol was increased upon PA conjugation. Previous biochemical experiments indicated that these PA-1,4-NQs are capable of inhibiting DNA human topoisomerase II-α (topo2α), a major enzyme involved in maintaining DNA topology. Herein, we applied molecular docking to investigate the binding of PA-1,4-NQs to the ATPase site of topo2α. The most active molecules preferentially bind at the ATP-binding site of topo2α, which is energetically favored by the conjugation with PA. Taken together, these findings suggested that the PA-1,4-NQ conjugates might represent potential molecules in the development of new drugs in chemotherapy for malignant brain tumors.

The botanical description of plants, classification and use of some of them as medicine to treat typical diseases of Brazilian regions may be accompanied by reports described in historical records and botanical expeditions of adventurers and research of physicians and pharmacists. These were primarily responsible for discoveries that are still remembered and rethought for the development of potential drugs from these plants. This work presents a list of plants and their applications and uses by different people with the evolution of history.

Full Text PDF Images References Journal of Endodontics Volume 39, Issue 10 , Pages 1226-1233, October 2013 A Survey of Dentists' Preferences for the Treatment of Teeth with Apical Periodontitis Amir Azarpazhooh, DDS, MSc, PhD , Thuan Dao, DDS, MSc, PhD, Rafael Figueiredo, DDS, MSc, Murray Krahn, MD, MSc, Shimon Friedman, DDS Abstract Introduction This study surveyed the preferences of Ontario, Canada dentists for teeth with apical periodontitis when selecting between retention via root canal treatment (RCT) and extraction without replacement, or replacement with implant-supported crowns (ISC), fixed, or removable partial prostheses. Methods A mail-out survey (census of Ontario endodontists, periodontists, prosthodontists, and oral and maxillofacial surgeons; n = 498, 40% response rate) and a Web-based survey (sample of Ontario general dentists; n = 1983, 15% response rate) were conducted. Participants ranked their treatment preferences for 4 clinical scenarios: an anterior or posterior tooth, without or with previous RCT. Associations between treatment preferences and covariates were explored by using bivariate and logistic regression analyses (P ≤ .05). Results For all 4 scenarios, the majority of participants preferred either RCT or ISC, whereas other treatment options were preferred by ≤3.1% of the participants in any professional registration category. A pattern of declining preference for RCT and increasing preference for ISC was noted across the scenarios, with significantly lower preference for RCT and higher preference for ISC associated with teeth needing repeated RCT compared with initial RCT (odds ratio [OR] = 3.3; confidence interval [CI], 2.5– 4.4). Preferences were significantly lower for RCT and higher for ISC among general dentists (OR = 6.4; CI, 2.3–17.6), prosthodontists (OR = 9.1; CI, 3.0–28.3), periodontists (OR = 18.3; CI, 6.4–51.6), and surgeons (OR = 30.1; CI, 10.8–86.6) when compared with endodontists. Conclusions More surveyed dentists preferred RCT than ISC for teeth with apical periodontitis requiring initial RCT than repeated RCT. The dentists' preferences were associated with their professional registration but not with other characteristics.

The present paper brings two different photochemical aspects of benzophenothiazine chemistry: (i) the use of microwave radiation to prepare three benzophenothiazines derivates; and (ii) the photophysical characterization of the isolated compounds from microwave reactions by absorption and emission spectroscopy supported by DFT calculations at B3LYP/6-31G(d,p)/PCM level. The microwave assistant reactions reduced the reactions times compared with the conventional methods, but gave the same regioselectivity. The DFT study of the ground and excited states by linear response and state specific TD-DFT, absorption and emission, vibronic resolved spectra and charge analysis showed a very good correlation with the experimental results, and point out the benzothiazine moiety as the key element of the photophysical activity.

In the last decade, the research works on microbial as a potential source of lipid for biodiesel production have been growing. In this work, the potential of a sludge from high-rate lagoons in urban sewage treatment, composed mainly by Chlorella sp., as oil source for biodiesel production, was studied. The potential of Chlorella sp. growth in photobioreactor under controlled conditions was also investigated. Low lipid content (up to 3%) was observed in both cases. The composition of both oils showed high amount of fatty acids and fatty acid based compounds, however there are also other non-fatty acid based lipids. Density and viscosity of biodiesel from biosolid oil were determined and the results showed that these physico-chemical properties do not match the specification required for biodiesel. The results showed that sewage sludge from Samambaia treatment station (DF, Brazil) and Chlorella sp. cultivated under the conditions described in this work are not potential sources of fatty material for biodiesel production.

Isatin methyl derivatives have several pharmacotherapeutic applications, such as antibacterial, antifungal, antiviral, anticonvulsants and anticancer activities. The electrochemical behaviours of thirteen isatin-substituted derivatives with different functional groups, such as isatin 1-morpholinomethyl, isatin 1-hydroxymethyl, and isatin 1-, 5- or 7-methyl, and their halogenated derivatives, in phosphate buffer pH = 7.2, at a glassy carbon electrode, by cyclic, differential pulse and square wave voltammetry, were investigated. The oxidation mechanism of all isatin derivatives occurred in two consecutive irreversible charge transfer pH-dependent reactions. The first anodic reaction was on the benzene ring, with the generation of one hydroxyl group attached to the ring, which was oxidized in the second step to para- and/or ortho-quinone derivatives, and/or polymeric products. The reduction mechanism of all isatin derivatives, was an irreversible cathodic process, dependent on pH and the presence/absence of attached halogenated groups. The isatin derivatives reduction, in the absence of halogens, caused the irreversible cleavage of the carbonyl group, at the position C3, in the heterocyclic ring, and, in the presence of halogens, the cathodic peak corresponded to the carbon-halogen bond reduction. The functional groups attached to the isatin ring at the 1-position, morpholinomethyl-, hydroxymethyl- and methylare not electroactive, and do not affect considerably the isatin derivatives redox mechanism, since the oxidation occurs at the benzene ring, and the reduction at the carbonyl C3-position.

The inhibitors of the enzymes tyrosine kinase (ITKs), also known by "tinibs", have been used as the most modern and effective tools in the treatment of several types of cancer. This article is a compilation of a huge series of tyrosine kinase inhibitors, recently approved or under clinical trials, containing in each of them information such as: the first chemical synthesis, the mechanism of action against cancer, clinical trials stage and price in the market.

Inhibitors of the enzymes tyrosine kinase, also known by the acronym tinib, have been used as the most modern and effective tools in the treatment of several types of cancer. This article is a compilation of a huge series of tyrosine kinase inhibitors, recently approved or under clinical evaluations, containing in each of them information such as: the first chemical synthesis, the mechanism of action against cancer, clinical trials stage, suppliers and price in the market.

Through dereplication strategies using gas chromatography-mass spectrometry (GC-MS) and ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS), the ethanol extract from Psycotria nemorosa leaves (Rubiaceae) showed to be composed of: cinnamic acid, dihydroactinidiolide, 4-hydroxy-β-ionone, phytol, isophytol, 4,8,12,16-tetramethylheptadecan- 4-olide, lupeol, a mixture of α/β-amyrin, the keto and acetylated derivatives, besides stigmast-4- en-3-one, campesterol, stigmasterol and γ-sitosterol by GC-MS. Likewise, by UFLC-MS/MS, the main compounds identified were: butin, resveratrol, rutin, kaempferol 7- O-β-D-glucopyranoside, deacetylasperuloside, epiloganin, hordenine, strictosidine, N-methyl-1,2,3,4-tetrahydro-β-carboline and N-formyl-tryptamine. The antinociceptive activity of the crude extract ant its fractions was reported.

Chagas' disease is a parasitic disease with unsatisfactory treatment, mainly in chronic stage.This study aimed to evaluate the trypanocidal activity and action mechanisms of α/β-amyrin and its semisynthetic derivatives, together with four isolated natural triterpenes, tested against trypomastigote and amastigote forms.The structure-activity relationship was suggested and cytotoxicity was measured.In general, greater polar compounds may have improved the selectivity to the protozoan.Action mechanisms were only performed for the amastigotes of Trypanosoma cruzi by evaluating the ultrastructural alterations, membrane permeability, mitochondrial membrane potential and cell volume, since the majority of compounds displayed promising antiamastigote activities.Triterpenes promoted changes on mitochondrial membrane potential and ultrastructural features that suggest autophagy processes.Both combinations between α/β-amyrin and 3-O-acetyl-11-oxo-α/β-amyrin and 3-O-acetyl-α/β-amyrin with benznidazole displayed synergistic effects against amastigotes and antagonistic effects on LLCMK 2 cells.The antiamastigote activities, chemical derivatization, drug combinations and action mechanisms revealed to be crucial approaches toward this chronic disease.

This work reports the use of an acid-activated Brazilian smectite natural clay-based catalyst in the esterification of fatty acids at atmospheric pressure and without a co-solvent. Conversion levels of 99%, 98%, 93% and 80% were reached for caprylic, lauric, stearic and oleic methyl esters, respectively, using 1:3 fatty acid/methanol molar ratio, heating bath at 100 degrees C after 4 h. A conversion level of 89% was achieved for methyl esters from a fatty acid residue of the palm oil refining industry in the same reaction condition. The acid-activated clay provided better performance than the commercial catalyst K-10. The effects of catalyst amount, temperature, fatty acid/alcohol molar ratio and time were investigated. The heating activation of the catalyst immediately before the catalytic test increased the conversion from 94% to 99% using 1:1.5 stearic acid/methanol molar ratio, heating bath at 100 degrees C after 4 h. The catalyst was reused five times. The conversion decreases less than 5% in the first three reuses. The smectite natural clay and the catalyst were characterized by X-ray fluorescence, X-ray diffraction, n-butylamine thermodesorption, nitrogen adsorption analysis, thermogravimetric analysis and differential thermal analysis. (C) 2016 Elsevier Ltd. All rights reserved.

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania and includes cutaneous, mucocutaneous and visceral clinical forms. The drugs currently available for leishmaniasis treatment are pentavalent antimonials, amphotericin B and miltefosine, which present high toxicity, elevated cost and development of parasite resistance. The natural products constitute an important source of substances with leishmanicidal potential. Here we evaluated in vitro the anti-Leishmania amazonensis activity of crude extracts of branches, leaves and fruits of Guatteria latifolia. The branch extract (GCE) exhibited promising leishmanicidal activity against promastigotes (IC50 51.7 μg/ml), and was submitted to fractionation guided by in vitro assays. Among the seven subfractions obtained, GF1 and GF2 were the most actives against promastigotes with IC50 25.6 and 16 μg/ml, respectively. Since GCE, GF1 and GF2 were not toxic for macrophages, next, we tested their effect on intracellular amastigotes, and the IC50 values obtained were, respectively 30.5, 10.4 and 7.4 μg/ml, after 24 h treatment. The selectivity index for GCE, GF1 and GF2 were >6.5, >19.2 and > 27, respectively. Additionally, GCE, GF1 and GF2 affected the division pattern of the promastigotes by increasing 6.7, 9.4 and 7-fold the cells in Sub-G0/G1 phase, and decreasing 1.6, 2.5 and 1.8-fold the cells in G0/G1 phase, respectively. To assess the GCE and GFs capacity to modulate microbicidal mechanisms of macrophages, nitric oxide (NO) and TNF-α production were tested. Our results indicated that at the IC50s GCE, GF1 and GF2 decreased NO production of infected macrophages stimulated with IFN-γ and LPS, besides, only GF1 decreased the production of TNF-α. Our data warrant further studies of GCE, GF1 and GF2 to identify active compounds against Leishmania parasites.

A simple methodology giving rise to a new series of isatin-porphyrin conjugates and corresponding intracyclized derivatives is described. Palladium-catalyzed amination reactions of iodinated isatin derivatives containing the 3-carbonyl group protected with ketal functionalities and 2-amino-5,10,15,20-tetraphenylporphyrinatonickel(II) was the used procedure. The combination of palladium catalysts and the phosphine ligand dicyclohexylphospino-2′,4′,6’-triisopropylbiphenyl (XPhos) led to isatin-porphyrin conjugates in good yields. Nevertheless, the use of palladium acetate even resulted on the formation of additional six membered fused ring compounds. This brings a new perspective to access quinolino[2,3,4-at]porphyrins, a set of compounds which are typically obtained by harsh Cadogan or thermal cyclization approaches.

This review focuses on synthetic strategies that have been established for the preparation of porphyrin-quinone conjugates of potential biological significance and as donor–acceptor compounds for electron transfer processes.