Luis Cezar Rodrigues

Bioactivities from Marine Algae of the Genus Gracilaria

Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted.

Flavonoids from Praxelis clematidea R.M. King and Robinson modulate bacterial drug resistance.

Chemical studies of Praxelis clematidea R.M. King & Robinson resulted in the isolation of six flavones: Apigenine, genkwanine, 7,4’-dimethylapigenin, trimethylapigenin, cirsimaritin and tetramethylscutellarein, which were tested for their toxicity against Staphylococcus aureus SA-1199B, a strain possessing the NorA efflux pump. Efflux pumps are integral proteins of the bacterial membrane and are recognized as one of the main causes of bacterial drug resistance, since they expel antibiotics from the cell. The inhibition of this transporter is one form of modulating bacterial resistance to antimicrobial drugs. The flavones tested did not show any significant antibacterial activity against the Staphylococcus aureus strain used, but were able to modulate bacterial drug resistance. This property might be related to the degree of lipophilicity of the flavones conferred by the methoxyl groups, since 4’,5,6,7 tetramethoxyflavone the most methoxylated compound, reduced the minimal inhibitory concentration of the drug 16-fold.

Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data

Aplysina is the best representative genus of the family Aplysinidae. Halogenated substances are its main class of metabolites. These substances contribute greatly to the chemotaxonomy and characterization of the sponges belonging to this genus. Due to their pharmacological activities, these alkaloids are of special interest. The chemistry of halogenated substances and of the alkaloids has long been extensively studied in terrestrial organisms, while the number of marine organisms studied has just started to increase in the last decades. This review describes 101 halogenated substances from 14 species of Aplysina from different parts of the world. These substances can be divided into the following classes: bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C), bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F), spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and dibromocyclohexadienes (J). A compilation of their 13C NMR data is also part of the review. For this purpose 138 references were consulted.

Antinociceptive Effect of Lupeol: Evidence for a Role of Cytokines Inhibition

The present study investigates the antinociceptive properties of lupeol in models of inflammatory and post‐operative pain, as well as its mechanisms of action. The effects of lupeol were tested against acetic acid‐induced writhing, formalin test, carrageenan‐induced hyperalgesia, and post‐operative pain model. Cytokine levels were determined by ELISA. Mice motor performance was evaluated in the rota rod and open‐field tests. Pre‐treatment of mice with lupeol (5–100 mg/kg IP) produced a dose‐related inhibition of writhing in mice. The maximal antinociception produced by lupeol (60 mg/kg) was unaffected in mice pre‐treated with yohimbine (α2 adrenoceptor antagonist; 2 mg/kg IP), L‐arginine (substrate for nitric oxide synthase; 600 mg/kg IP), glibenclamide (the KATP‐channel blocker; 2 mg/kg IP), and methysergide maleate (serotoninergic receptors antagonist; 5 mg/kg IP). Furthermore, lupeol (25–100 mg/kg) inhibited the late phase of formalin test. Pre‐treatment with lupeol (50 and 100 mg/kg) inhibited the hyperalgesia and the local increase in tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels induced by carrageenan. In contrast, lupeol did not inhibit the post‐operative pain. Lupeol‐treated mice did not show any motor performance alterations or apparent systemic toxicity. Our results demonstrate that lupeol has consistent antinociceptive properties during inflammatory pain, but not post‐operative pain, acting through the inhibition of IL‐1β and TNF‐α production. Copyright

Synthesis, acute toxicity and anti-inflammatory effect of bornyl salicylate, a salicylic acid derivative

Bornyl salicylate (BS) is a salicylic derivative, obtained by sterification of salicylic acid and monoterpene (-)-borneol, and its topical use in inflammatory diseases was described in the early 20th century. It is also known that borneol presents neuroprotective, genoprotective and analgesic properties. The purpose of this study was to evaluate BS in experimental models of acute inflammation. The toxicity of BS was analyzed by measuring water and food intake, weight, mortality and weight of main organs. To assess its anti-inflammatory effect, BS-treated mice were challenged with carrageenan, prostaglandin E2 (PGE2), bradikynin (BK) or histamine (HIS)-induced paw edema, zymosan-induced peritonitis and vascular permeability induced by acetic acid. Nitric oxide (NO) production was analyzed in peritoneal macrophage cultures. There was no sign of acute toxicity of BS in male and female mice. Furthermore, treatment with BS was significantly (p < 0.05) effective in reducing paw edema induced by carrageenan in early and late phases; this effect was related to PGE2 and BK, but HIS independent. Neutrophil migration and cytokine release (TNF-α, IL-1β and IL-6) induced by zymosan and fluid leakage induced by acetic acid were also reduced in BS-treated animals. In vitro, BS (10 µg/mL) reduced NO production in LPS-stimulated macrophages. These data suggest that BS has an anti-inflammatory effect, which is related, at least in part, with decrease of mediators as PGE2, NO and pro-inflammatory cytokines. However, further studies should be done to explore its potential as an anti-inflammatory drug.

Synthesis, toxicity study and anti-inflammatory effect of MHTP, a new tetrahydroisoquinoline alkaloid.

Abstract The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol (MHTP) was synthesized to prospect new compounds with therapeutic properties. Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP pre-treatment (2.5–10 mg/kg) showed antiedematogenic effect (p < 0.05) in carrageenan-induced paw edema by inhibiting the PGE2 action independently of mast cell degranulation or histamine activity. MHTP also diminished (p < 0.01) total leukocyte migration in 41.5% into peritoneal cavity during carrageenan-induced peritonitis, reducing polymorphonuclear cells (PMNs) (59.6%) and proteins levels (29.4%). MHTP in an experimental model of acute lung injury inhibited (p < 0.001) total inflammatory cell migration into the lungs and PMNs in 58% and 67.5%, respectively. Additionally, MHTP did not present cytotoxicity at concentrations of 10, 25 or 50 μM but decreased (p < 0.001) the NO production in 24%, 47% and 39%, respectively. The alkaloid also reduced (p < 0.001, in lipopolysaccharide (LPS)-stimulated macrophages (1 μg/mL), IL-1β, IL-6 and IL-10 levels in 35.7%, 31.0% and 33.4%, respectively. The results obtained in this study allow us to conclude that the inedited synthetic alkaloid, MHTP has anti-inflammatory effect by inhibiting PGE2 function as well as inhibiting inflammatory cell migration to the inflamed site and attenuated the acute lung injury disease by inhibiting the migration of neutrophil to the lung. However, further studies will be carried out to demonstrate the mechanisms of action of the molecule and explore its potential as a future drug to treat inflammatory processes.

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono- and Dimethyl Ethers.

The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3[Fe(CN)6]) and NH3 · H2O. The partial methoxylation of DHDE with MeI and K2CO3 mainly resulted in the molecular‐shaped monomethyl ether (DHDE‐1MeO) and its dimethyl ether derivative (DHDE‐2MeO). The products from the reactions were characterized by 1H‐ and 13C‐NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 μg ml−1) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 μg ml−1). Based on in vitro bioassays, DHDE‐1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one‐step synthesis of this monomethoxylated compound can be considered to be a cost‐effective and environmentally friendly method with a short reaction time.

Synthesis of natural phenylpropanoid esters via conventional chemical reactions

1 Post-Graduate Program in Natural Products and Bioactives, Federal University of Paraíba, João Pessoa, 58051-900, PB, Brazil 2 Department of Chemistry, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, 35017, Spain Department of Biotechnology, Federal University of Paraíba, João Pessoa, 58051-900, PB, Brazil Post-Graduate Program in Development and Technological Innovation in Medicines, Federal University of Paraíba, João Pessoa, 58051-900, PB, Brazil