Conjugation with polyamines enhances the antitumor activity of naphthoquinones against human glioblastoma cells.

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.

Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction.

Geissospermum vellosii (Pao pereira) is a Brazilian tree whose stem barks are rich in indole alkaloids that present intense anticholinesterase activity. The present study evaluated the effects of a stem bark fraction (PPAC fraction) and ethanolic extract (EE) of Pao pereira in classic murine models of inflammation and pain. The EE and PPAC fraction, both at a dose of 30 mg/kg, significantly reduced mice abdominal constriction induced by acetic acid by 34.8% and 47.5%, respectively. In the formalin test, EE (30 mg/kg) and PPAC fraction (30 and 60 mg/kg) inhibited only the second phase, by 82.8%, 84.9% and 100%, respectively. Compared with indomethacin, similar doses of EE or PPAC fraction were approximately twice as effective in causing antinociception. PPAC fraction was not effective in the hot plate test but reduced the inflammatory response at the second (50.6%) and third (57.8%) hours of rat paw edema induced by carrageenan. Antihyperalgesic activity was observed within 30 min with a peak at 2 h (60.1%). These results demonstrate that compounds in PPAC fraction have anti-inflammatory and antinociceptive activity by a mechanism apparently unrelated to the opioid system. Regardless of similar responses to indomethacin, the effects of PPAC fraction are mainly attributed to acetylcholine actions.

Anthranilic acids from isatin: an efficient, versatile and environmentally friendly method.

This paper describes the preparation of a series of 16 anthranilic acids in yields ranging from 51 to 97%, by treating the isatins with NaOH and H2O2. Independently of the nature of the substituent on the aromatic ring, the reactions were complete in 15 min at room temperature, whereas those of isatins containing a substituent on the nitrogen atom required longer reaction time for completion (45 min) under the same reaction conditions.

New trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents.

According to the World Health Organization, half of the World's population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF3 group substituted at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC50 values ranging from 0.023 to 20 µM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.

The mechanism of Sandmeyer's cyclization reaction by electrospray ionization mass spectrometry.

Using electrospray ionization (tandem) mass spectrometry (ESI-MS(/MS)) spectrometric experiments, the Sandmeyer reaction was monitored on-line, and key intermediates were intercepted and characterized for the first time. The mechanistic information provided by on-line ESI-MS(/MS) is in accordance with Sandmeyer's proposal, and was made possible by coupling a microreactor on-line to the ESI ion source, which allowed reactions to be screened from 0.7-2.0 s, identifying and characterizing all intermediates that were formed and consumed during the reaction.

Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.

Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 µM) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 µM MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.

Anthraquinones from the bark of Senna macranthera.

2-acetyl physcion (2-acetyl-1,8-dihydroxy-6-methoxy-3-methyl-9,10-anthraquinone, 2), a rare anthraquinone, was isolated from Senna macranthera var. nervosa (Vogel) H.S. Irwin & Barneby (Fabaceae). The chemical structure was elucidated and all (1)H and (13)C NMR chemical shifts were assigned by NMR one- ((1)HNMR, {(1)H}-(13)CNMR, and APT-(13)CNMR) and two (COSY, NOESY, HMQC and HMBC) dimensional of this natural compound. Furthermore, the minor anthraquinones chrysophanol (3), chrysophanol-8-methyl ether (4) and physcion (5) were characterized by GC-MS analysis. The occurrence of the anthraquinones 3-5 confirms that S. macranthera is a typical representative of the genus Senna.

Synthesis of alpha- and beta-pyran naphthoquinones as a new class of antitubercular agents.

A series of alpha- and beta-pyran naphthoquinones (lapachones) have been synthesized and evaluated for their in-vitro antibacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar-Blue susceptibility test; the activity was expressed as the minimum inhibitory concentration (MIC) in microg/mL. The synthetic methodology consisted of the formation of methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes. These o-QMs then undergo facile hetero Diels-Alder reactions with dienophiles in aqueous ethanol media. Some naphthoquinones exhibited inhibition with MIC values of 1.25 microg/mL, similar to that of pharmaceutical concentrations currently used in tuberculosis treatment. These results justify further research into the value of these quinones as part of an original treatment for tuberculosis.

Synthetic lapachol derivatives relax guinea-pig ileum by blockade of the voltage-gated calcium channels.

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, alpha-norlapachone, beta-norlapachone and hydro-hydroxy-norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (Ca(V)). As the tonic component this contraction is maintained mainly by the opening of the Ca(V), we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD'2 = 4.99), alpha-norlapachone (pD'2 = 4.49), beta-norlapachone (pD'2 = 6.33), and HH-norlapachol (pD'2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As beta-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 +/- 0.30) x 10(-5) M] suggests that the Ca2+ channel involved belongs to the type L (Ca(V)1.2). In addition, in the functional level, the spasmolytic effect of beta-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.

(2E)-N-(3,5-Dibromo-4-methoxy-phen-yl)-2-(hydroxy-imino)acetamide.

The title compound, C(9)H(8)Br(2)N(2)O(3), is planar (r.m.s. deviation = 0.030 Å) with the exception of the terminal methyl group which lies out of the plane [1.219 (3) Å]. The conformation about the C=N double bond [1.268 (3) Å] is E. An intra-molecular N-H⋯N hydrogen bond occurs. Linear supra-molecular chains along the b axis mediated by O-H⋯O hydrogen-bonding inter-actions feature in the crystal structure. These chains are also stabilized by weak C-H⋯N contacts.

Acute effect of Copaifera reticulata Ducke copaiba oil in rats tested in the elevated plus-maze: an ethological analysis.

OBJECTIVES: Copaiba oil oleoresin exuded from Copaifera reticulata Ducke (CRD) is commonly used in anti-inflammatory, healing and anti-tumoral folk medicines. The purpose of this study was to investigate the putative anxiolytic effect of acute administration of CRD. METHODS: CRD was administered (100, 400 and 800 mg/kg, p.o.) to male Wistar rats submitted to the elevated plus-maze model of anxiety using an ethopharmacological analysis. KEY FINDINGS: In comparison with control rats, CRD increased the percentage of entries in the open arms over the entire dose range tested (vehicle, 33.6 +/- 4.5; CRD 100 mg/kg, 44.67 +/- 3.68; CRD 400 mg/kg, 47.2 +/- 2.3; CRD 800 mg/kg, 50.7 +/- 2.2) and the percentage of time spent in the open arms of the elevated plus-maze at the highest dose (800 mg/kg) (vehicle, 26.4 +/- 5.7; CRD 800 mg/kg, 52.0 +/- 2.7). A standard anxiolytic, diazepam (3 mg/kg, p.o.), was used as a positive control. In a similar way, diazepam increased the percentage of entries and time spent in the open arms when compared with vehicle (% open entries: vehicle, 45.4 +/- 1.3; diazepam, 50.7 +/- 1.9; % time spent in open arms: vehicle, 28.2 +/- 0.9; diazepam, 38.9 +/- 1.2). Regarding ethological measures, CRD at the highest dose (800 mg/kg) reduced peeping out (anxiety-related behaviour) (vehicle, 3.1 +/- 0.6; CRD, 0.9 +/- 0.2) and increased end-arm activity (vehicle, 0.2 +/- 0.2; CRD, 2.0 +/- 0.4), indicating an enhanced tendency of the rats to explore actively the potentially dangerous areas of the maze. Diazepam decreased peeping out (vehicle, 3.3 +/- 0.3; diazepam, 1.0 +/- 0.2) and flat-back approach (vehicle, 0.8 +/- 0.2; diazepam, 0.2 +/- 0.1) and increased end-arm activity (vehicle, 0.3 +/- 0.1; diazepam, 2.5 +/- 0.3) and head-dipping (vehicle, 8.2 +/- 0.4; diazepam, 12.0 +/- 0.5). CONCLUSIONS: These data showed, for the first time, that acute treatment with CRD copaiba oil produced a dose-dependent anxiolytic-like effect over the dose range tested, on conventional and ethological parameters, without adversely affecting general activity levels.

Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking.

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.

Vasodilatory activity of novel carbamate derivatives of isatin.

Isatin (1H-indole-2,3 dione) is an endogenous compound that may act as a physiological regulator of muscle contraction by reducing cGMP production by inhibition of guanylyl cyclase (GC) activity. Intracellular cGMP levels can regulate the contractile response of smooth muscle. Therefore, in the present study we investigated the effects of seven novel carbamate derivatives of isatin, namely C1-C7, on the contractility of aortic rings from Wistar rats. Carbamates C1 and C6 most effectively promoted endothelium-dependent relaxation of aortic rings pretreated with 10 micromol/L phenylephrine (PE) to induce contraction. The concentration of the C1 and C6 carbamates necessary to reduce PE-induced aortic contraction by 50% (IC(50)) was 5.6 +/- 1.0 and 48.4 +/- 3.4 micromol/L, respectively. Carbamate derivative-induced vasodilation required an intact endothelium, which is responsible for nitric oxide (NO) release. Pretreatment of rings with 100 micromol/L naloxone or 10 micromol/L atropine prevented the C1- and C6-mediated vascular relaxation, indicating that the vasodilatory activity was dependent on the activation of opioid or muscarinic receptors, respectively. The results of our studies provide insights into the role of novel carbamates in the regulation of vascular tone. Carbamates could stimulate NO synthesis, which induces vasodilation primarily by stimulation of GC and cGMP production. Taken together, our findings suggest that carbamate derivative-induced vasodilation may be considered an alternative treatment for primary and/or secondary hypertension.

Effect of Brazilian copaiba oils on Leishmania amazonensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaiba oil has been used in folk medicine since the 19th century. The use of copaiba oils to treat leishmaniasis is cited in several ethnopharmacological studies. Nevertheless, the potential antileishmania of copaiba oils had not been studied. AIM OF THE STUDY: Eight different kinds of Brazilian copaiba oils were screened for antileishmanial activity. MATERIALS AND METHODS: The antiproliferative effect of copaiba oil on promastigote and amastigote axenic were determined. To determine the survival index peritoneal macrophage were infected with promastigotes of Leishmania amazonensis and treated with copaiba oil. The cytotoxic effect of copaiba oil was assessed on macrophage strain J774G8 by assay of sulforhodamine B. RESULTS: Copaiba oils showed variable levels of activity against promastigote forms with IC(50) values in the range between 5 and 22microg/mL. The most active oil was that from Copaifera reticulata (collected in Pará State, Brazil) with IC(50) values of 5, 15, and 20microg/mL for promastigote, axenic amastigote and intracellular amastigote forms, respectively. Amphotericin B showed IC(50) of 0.058 and 0.231microg/mL against promastigote and amastigote forms, respectively. Cytotoxicity assay showed that this copaiba oil obtained from Copaifera reticulata showed low cytotoxicity against J774G8 macrophages. CONCLUSION: Copaiba oils showed significant activity against the parasite Leishmania amazonensis.

Anisotropic and hydrogen bonding effects in phenylglyoxamides and mandelamides: theoretical and NMR conformational evaluation.

Interesting anisotropic effects were observed for phenylglyoxamides and their respective mandelamides. Such effects were observed in experimental (1)H and (13)C NMR (in CDCl(3), CD(3)OD, and DMSO-d(6) solvents) and in some cases with good correlation to theoretical (1)H and (13)C NMR DFT-GIAO (B3LYP/6-311++G**//B3LYP/6-31G*) calculations. A systematic conformational analysis of these compounds was performed in a two-step methodology, using PM3 and DFT (B3LYP/6-31G*) calculations; with good accomplishment and computational time economy. It was observed that intramolecular hydrogen bonding plays a significant role in the conformation of such compounds. Finally, a geminal nonequivalence of an N-CH(2) moiety, in one of the alkyl side chain (R1 = R2), was found for the tertiary mandelamides studied.

Elucidating the mass spectrum of the retronecine alkaloid using DFT calculations.

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.

New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity.

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.

Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line.

Isatin is a versatile compound with a diversity of effects. We designed to investigate the inhibitory effect of isatin derivatives on lipopolysaccharide/interferon-gamma-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, production of prostaglandin E(2) (PGE(2)), nitric oxide (NO), tumor necrosis factor (TNF-alpha), and their capacity to scavenge NO. Isatins inhibit TNF-alpha production and iNOS and COX-2 protein expression resulting on reduced levels of NO and PGE(2). Our results indicate isatin and it derivatives as inhibitors of iNOS and COX-2 enzymes, which might be used as anti-inflammatory and antitumoral agents.

Sedative-hypnotic profile of novel isatin ketals.

Isatin (1H-indol-2,3-dione) is an endogenous compound found in many tissues and fluids. Isatin and its derivatives exert pharmacological effects on the central nervous system, including anxiogenic, sedative and anticonvulsant activities. Two new groups of isatin derivatives were synthesized (nine dioxolane ketals and nine dioxane ketals) and studied for their sedative, hypnotic and anesthetic effects using pentobarbital-induced sleeping time, locomotor activity evaluation and intravenous infusion. The dioxolane ketals were more potent than dioxane ketals for inducing sedative-hypnotic states, causing up to a three-fold increase in pentobarbital hypnosis. The dioxolane ketals produced sedation, demonstrated by decreased spontaneous locomotor activity in an open field. Hypnosis and anesthesia were observed during intravenous infusion of 5'-chlorospiro-[1,3-dioxolane-2,3'-indolin]-2'-one (T3) in conscious Wistar rats. Complete recovery from hypnosis and anesthesia required 39.1+/-7.3 and 6.8+/-2.4 min, respectively. Changes in hemodynamic parameters after infusion of 5.0 mg/kg/min were minimal. These findings suggest that these new isatin derivatives represent potential candidates for the development of new drugs that act on the central nervous system and may lead to a new centrally acting anesthetic with no toxic effects on the cardiovascular or respiratory systems.

Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne--a comparative study.

Copaiba oil is an oleoresin obtained from the Copaifera L. genus (Leguminoseae) commonly featured in anti-inflammatory recipe prescribed by Amazonian traditional medical practitioners and featured in Europe and North America pharmacopeias of the past. Chemical and anti-inflammatory activity investigations from the copaiba oils obtained from Copaifera multijuga Hayne, Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke species have proved that, although similar, these oleoresins possess varied composition and anti-inflammatory activity. Chromatographic studies showed that the main compound among sesquiterpenes was beta-caryophyllene (57.5, 19.7 and 40.9%, respectively), followed by alpha-humulene, alpha-copaene, alpha-bergamotene, delta-cadinene, with different amounts in each oleoresin. Among the diterpenes, copalic acid was the main component from Copaifera multijuga Hayne (6.2%) and was found in all the oleoresins studied. In Copaifera cearensis Huber ex Ducke, clorechinic (11.3%) and hardwickiic acids (6.2%) were the major diterpenes while kaurenoic (3.9%) and kolavenic acids (3.4%) predominated in Copaifera reticulata Ducke. The pharmacologic effects of the three oleoresins were evaluated in vitro by measuring the NO production by murine macrophages and in vivo using the zymosan induced pleurisy model in mice. The Copaiba Oil from Copaifera multijuga Hayne (100 mg/kg) was the most potent, inhibiting both NO production and the pleurisy induced by zymosan. The oleoresins from Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke were also able to inhibit NO production and the pleurisy but with less intensity.