Physical-chemical and ecotoxic evaluation of different deep eutectic solvents for green analytical applications.

The search for new analytical methods is a latent reality in the so-called green analytical chemistry area, which aims at correlating analytical demands to environmental issues. Among the approaches used, it is possible to highlight green solvents as substitutes to the dangerous and conventional organic solvents as the most prominent alternative for this purpose. In the last few years, the amount of research focused on the usage of deep eutectic solvents (DESs) has been growing as an alternative to these issues. Thus, this work aimed to investigate the main physical-chemical and ecotoxical properties of seven different DESs. The results showed that DESs' evaluated properties are influenced by the chemical structure of their precursors, which may regulate DESs' viscosity, superficial tension, and antagonistic action against vegetable tissues and microbial cells. The constatations pointed here introduce a new perspective about the conscious usage of DESs on a green analytical point of view.

ISCOM-Matrices Nanoformulation Using the Raw Aqueous Extract of Quillaja lancifolia (Q. brasiliensis).

Quillaja saponins have an intrinsic capacity to interact with membrane lipids that self-assembles in nanoparticles (immunostimulating complexes or ISCOM-matrices) with outstanding immunoadjuvant activity and low toxicity profile. However, the expensive and laborious purification processes applied to purify Quillaja saponins used to assemble ISCOM-matrices show an important drawback in the large-scale use of this vaccine adjuvant. Thus, in this study, we describe a protocol to appropriately formulate ISCOM-matrices using the raw aqueous extract (AE) of Quillaja lancifolia leaves. In the presence of lipids, AE was able to self-assemble in nanostructures that resembles immunostimulating complexes (ISCOM). These negatively charged nanoparticles of approximately 40 nm were characterized by transmission electron microscopy and dynamic light scattering. In addition, well-known saponins with remarkable immunoadjuvant activity, as QS-21, were detected into nanoparticles. Thus, the easier, robust, cheaper, and environmentally friendly method developed here may be an alternative to the classical methods for ISCOM-matrices production that use high-purified saponins.

Antiviral activity of ouabain against a Brazilian Zika virus strain.

Zika virus (ZIKV) is an emerging arbovirus associated with neurological disorders. Currently, no specific vaccines or antivirals are available to treat the ZIKV infection. Ouabain, a cardiotonic steroid known as Na+/K+-ATPase inhibitor, has been previously described as an immunomodulatory substance by our group. Here, we evaluated for the first time the antiviral activity of this promising substance against a Brazilian ZIKV strain. Vero cells were treated with different concentrations of ouabain before and after the infection with ZIKV. The antiviral effect was evaluated by the TCID50 method and RT-qPCR. Ouabain presented a dose-dependent inhibitory effect against ZIKV, mainly when added post infection. The reduction of infectious virus was accompanied by a decrease in ZIKV RNA levels, suggesting that the mechanism of ZIKV inhibition by ouabain occurred at the replication step. In addition, our in silico data demonstrated a conformational stability and favorable binding free energy of ouabain in the biding sites of the NS5-RdRp and NS3-helicase proteins, which could be related to its mechanism of action. Taken together, these data demonstrate the antiviral activity of ouabain against a Brazilian ZIKV strain and evidence the potential of cardiotonic steroids as promising antiviral agents.

A late-stage diversification via Heck-Matsuda arylation: Straightforward synthesis and cytotoxic/antiproliferative profiling of novel aryl-labdane-type derivatives.

In the current study a late-stage diversification of unactivated olefins labd-8(17)-en-15-oic acid (1a) and methyl labd-8(17)-en-15-oate (1b) via Heck-Matsuda arylation is described. The reaction provided straightforward and practical access to a series of novel aryl-labdane-type derivatives (HM adducts 3a-h) in moderate to good yields in a highly regio- and stereoselective manner at room temperature under air atmosphere. The cytotoxic activity of these compounds was investigated in vitro against three different human cell lines (THP-1, K562, MCF-7). Of these, HM adduct 3h showed a selective effect in all cancer cell lines tested and was selected for extended biological investigations in a leukemia cell line (K562), which demonstrated that the cytotoxic/antiproliferative activity observed in this compound might be mediated by induction of cell cycle arrest at the sub-G1 phase and by autophagy-induced cell death. Taken together, these findings indicate that further investigation into the anticancer activity against chronic myeloid leukemia from aryl-labdane-type derivatives may be fruitful.

Essential oil composition and antinociceptive activity of Thymus capitatus.

CONTEXT: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties. OBJECTIVE: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify and quantify the constituents of the T. capitatus EO. The antinociceptive activity was evaluated in vivo by the glutamate-induced nociception model in male Swiss mice (25 g), at doses of 3, 6 and 12 mg/kg, 1 h before evaluation of the licking time response (0-15 min). The mechanism of T. capitatus EO (1-500 µg/mL) on the isolated nerve excitability of Wistar rat (300 g) was assessed by the single sucrose technique. RESULTS AND DISCUSSION: The EO of T. capitatus presented 33 components, mainly monoterpenes and sesquiterpenes, carvacrol (ca. 80%) was its major constituent. T. capitatus EO induced antinociception in orally treated mice (3, 6, and 12 mg/kg) reducing the licking time from control (100.3 ± 11.9 s) to 84.8 ± 12.2, 62.7.6 ± 9.9, and 41.5 ± 12.7 s, respectively (n = 8; p < 0.05). Additionally, we have demonstrated that T. capitatus EO (500 µg/mL) decreased the compound action potential amplitude (VCAP) of about 80.0 ± 4.3% from control recordings (n = 4; p < 0.05). Such activity was presumably mediated through a voltage-gated Na+ channels. CONCLUSIONS: The present study demonstrated the antinociceptive activity of Thymus capitatus essential oil, which acts via peripheral nervous excitability blockade.

Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives.

In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 2-7. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8a-c and aminoguanidine hydrochloride accessed by microwave irradiation. The aminoguanidine 5, 6 and 7 were prepared by reduction of guanylhydrazone 2-4 with sodium cyanoborohydride (94% yield of 5, and 100% yield of 6 and 7). The aromatic ketones 8a-c were prepared from the Barbier reaction followed by the Prins cyclization reaction (two steps, 63%-65% and 95%-98%). Cytotoxicity studies have demonstrated the effects of compounds 2-7 in various cancer and normal cell lines. That way, we showed that these compounds decreased cell viabilities in a micromolar range, and from all the compounds tested we can state that, at least, compound 3 can be considered a promising molecule for target-directed drug design.

Essential oils components as a new path to understand ion channel molecular pharmacology.

The discovery and development of new drugs targeting voltage-gated ion channels are important for treating a variety of medical conditions and diseases. Ion channels are molecular nanostructures expressed ubiquitously throughout the whole body, and are involved in many basic physiological processes. Over the years, natural products have proven useful in the pharmacological assessment of ion channel structure and function, while also contributing to the identification of lead molecules for drug development. Essential oils are complex chemical mixtures isolated from plants which may possess a large spectrum of biological activities most of them of clinical interest. Among their bioactive constituents, terpenes are small to medium-sized components and belong to different chemical groups. Various reports have drawn our attention to the fact that terpenes are novel compounds targeting voltage-gated ion channels. The purpose of this review is to provide a focused discussion on the molecular interaction between monoterpenes and phenylpropenes with voltage-gated ion channels in different biological scenarios.

Antinociceptive activity of (-)-carvone: evidence of association with decreased peripheral nerve excitability.

(-)-Carvone is a monoterpene ketone that is the main active component of Mentha plant species like Mentha spicata. This study aimed to investigate the antinociceptive activity of (-)-carvone using different experimental models of pain and to investigate whether such effects might be involved in the nervous excitability elicited by others monoterpenes. In the acetic acid-induced writhing test, we observed that (-)-carvone-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg was administered. It was also demonstrated that (-)-carvone inhibited the licking response of the injected paw when 100 and 200 mg/kg was administered (i.p.) to mice in the first and second phases of the formalin test. Since naloxone (5 mg/kg, s.c.), an opioid antagonist, showed no influence on the antinociceptive action of (-)-carvone (100 mg/kg), this suggested nonparticipation of the opioid system in the modulation of pain induced by (-)-carvone. Such results were unlikely to be provoked by motor abnormality, since (-)-carvone-treated mice did not exhibit any performance alteration on the Rota-rod apparatus. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and observed that (-)-carvone (10 mM) was able to reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 50% from control recordings. We conclude that (-)-carvone has antinociceptive activity associated with decreased peripheral nerve excitability.

Detection of oral streptococci in dental biofilm from caries-active and caries-free children.

This work correlated the presence of oral streptococci in dental biofilm with clinical indexes of caries and oral hygiene in caries-active and caries-free children. S. mutans and/or S. sobrinus in the dental biofilm does not indicate a direct risk for developing dental caries.