Petrônio Athayde Filho | UFPB - Universidade Federal da Paraíba (original) (raw)

Papers by Petrônio Athayde Filho

Zeitschrift für Naturforschung C, 2007

Crude ethanolic extract, lignoid fraction and the purified compound yangambin were obtained from ... more Crude ethanolic extract, lignoid fraction and the purified compound yangambin were obtained from Ocotea duckei (Lauraceae) and their antileishmanial activity was tested against promastigote forms of Leishmania chagasi and Leishmania amazonensis cultivated in Schneider medium, supplemented with 20% of fetal bovine serum. All substances presented antileishmanial activity with IC50 values of 135.7 μg/mL for the crude ethanolic extract, 26.5 μg/mL for the lignoid fraction and 49.0 μg/mL for yangambin on L. chagasi. For L. amazonensis the IC50 values were 143.7 μg/mL, 48.2 μg/mL and 64.9 μg/mL for the crude ethanolic extract, the lignoid fraction, and the purified compound yangambin, respectively. The crude ethanolic extract, lignoid fraction, and yangambin caused an inhibition higher than Glucantime“, a reference drug used for the treatment of leishmaniasis.

Acta pharmaceutica (Zagreb, Croatia), 2014

Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment ... more Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4-thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the title compounds was elucidated by elemental analysis, IR, (1)H and (13)C NMR spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated for their ex vivo spasmolytic potential on four isolated smooth muscles (rat aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine. Some of the compounds exhibited potent spasmolytic activity equal to or stronger than scopolamine.

J. Phys. Chem. C , 2018

The first hyperpolarizabilities of the mesoionic compounds (MICs) 2-(4-chlorophenyl)-3-methyl-4-p... more The first hyperpolarizabilities of the mesoionic compounds (MICs) 2-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-5-thiolate (MIC-1), 2-(4-chlorophenyl)-3-methyl-4-(4-methylphenyl)-1,3-thiazolium-5-thiolate (MIC-2), and (2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1,3-thiazolium-5-thiolate) (MIC-3), dissolved in dimethyl sulfoxide (DMSO), are reported here for the first time to our knowledge. Hyper-Rayleigh scattering experiments were performed with an excitation source operating at λ = 1180 nm (ω = 8475 cm −1). The measured hyperpolarizability, β(2ω), was used to calculate the static hyperpolarizability, β(0), by applying the classical two-level model. The values obtained for β(0) were 10.1 × 10 −30 esu (MIC-1), 8.7 × 10 −30 esu (MIC-2), and 10.4 × 10 −30 esu (MIC-3) which are smaller than previous theoretical predictions that did not consider features related to the liquid phase. ■ INTRODUCTION Recent developments of nonlinear (NL) optical materials are concerned with the design of new systems with enhanced second-and third-order optical properties aiming their uses in optoelectronic devices, 1,2 all-optical limiters, 3 and THz imaging and spectroscopy, 4 among other applications. Important works have been reported with focus on the exploitation of new organic molecules because they present large NL optical coefficients, fast response times, straightforward synthesis, and processability. In particular, molecules with electronic push−pull systems, which give rise to π-electrons delocalization, present large optical hyperpolarizabilities and fast response for nonresonant excitation. 5−12 Organic molecules formed by push−pull systems have three components; an electro-acceptor group (R A), an electron-donor group (R D) and a π-conjugated spacer to link the R A and R D. 9,10 The goal is to engineer the components in order to maximize the optical hyperpolarizabilities. Among the push−pull organic systems known, the mesoionic compounds (MICs) deserve special attention because of their remarkable physical and chemical properties that enable applications as antioxidant, 13 anti-inflammatory, 14 antibacterial, 15 and antitumor sumstances, 16 as well as the large NL optical susceptibility as already proposed 17−19 and experimentally demonstrated. 20−22 Indeed, the MICs' properties point to NL biophotonics as a possible avenue for future applications. MICs are planar five-membered heterocyclic betaines, with at least one side-chain whose atom is also in the ring plane where the positive and negative charges are separated and delocalized within a π-electrons system that originate permanent electric dipole moments of ≈5 D. The region, which includes the side chain atom, is associated with highest occupied molecular orbital (HOMO) and a negative π-charge, while the other is associated with lowest unoccupied molecular orbital (LUMO) and a positive π-charge. 18 The molecules are neutral, they present π-electron delocalization, and they are composed of resonant (mesomeric) structures. In previous theoretical studies the potential of MICs for NL optics was considered on the basis of their high hyper-polarizability values, their stability and the possibility of improving their optical response by manipulation of their chemical structure. 17,19 The studies revealed that certain MICs present relatively high third-order NL optical response in the visible and near-infrared regions that were verified in experiments with pulsed lasers operating in various temporal regimes. For example, two-photon absorption cross sections in

Biomedicine & Pharmacotherapy, 2020

Structural diversity characterizes natural products as prototypes for design of lead compounds. T... more Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and mi-cronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC 50 (lethal concentration 50%) higher than 100 μg/mL. On the acute toxicity assay in mice, LD 50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1β, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.

A B S T R A C T Rationale: Development and progression of cardiovascular diseases, including hype... more A B S T R A C T Rationale: Development and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance. In this study, we evaluated NO release capability and cardiovascular effects of the newly synthesized organic nitrate 1, 3-bis (hexyloxy) propan-2-yl nitrate (NDHP). Methods: A combination of in vitro and in vivo approaches was utilized to assess acute effects of NDHP on NO release, vascular reactivity and blood pressure. The therapeutic value of chronic NDHP treatment was assessed in an experimental model of angiotensin II-induced hypertension in combination with NOS inhibition. Results: NDHP mediates NO formation in both cell-free system and small resistance arteries, a process which is catalyzed by xanthine oxidoreductase. NDHP-induced vasorelaxation is endothelium independent and mediated by NO release and modulation of potassium channels. Reduction of blood pressure following acute intravenous infusion of NDHP was more pronounced in hypertensive rats (two-kidney-one-clip model) than in normotensive sham-operated rats. Toxicological tests did not reveal any harmful effects following treatment with high doses of NDHP. Finally, chronic treatment with NDHP significantly attenuated the development of hypertension and endothelial dysfunction in rats with chronic NOS inhibition and angiotensin II infusion. Conclusion: Acute treatment with the novel organic nitrate NDHP increases NO formation, which is associated with vasorelaxation and a significant reduction of blood pressure in hypertensive animals. Chronic NDHP treatment attenuates the progression of hypertension and endothelial dysfunction, suggesting a potential for therapeutic applications in cardiovascular disease.

Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were f... more Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR), 1 H and 13 C nuclear magnetic resonance (NMR). The compounds were evaluated in an in silico study and showed strong to moderate antibacterial activity against several strains of Staphylococcus aureus. In particular, three compounds exhibited excellent antibacterial activity, with minimum inhibitory concentrations (MICs) between 16 and 64 μg mL-1. Furthermore, two of the nine compounds showed antifungal activity, with MIC of 1024 and 512 μg mL-1. In silico studies of the parameters of Lipinski's rule of five indicate that these compounds have potential to be new drug candidates.

A B S T R A C T In this report, we describe the synthesis and characterization of 1,3-bis(hexylox... more A B S T R A C T In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.

Journal of Thermal Analysis and Calorimetry, 2005

Page 1. Introduction The tropical shrub Urucum internationally known as annatto (Bixa orellana L.... more Page 1. Introduction The tropical shrub Urucum internationally known as annatto (Bixa orellana L.) is a small tree with predom-inant occurrence in the South American regions (par-ticularly in Brazil). Bixin is the major component ...

We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate ... more We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane
Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic
treatment with HEX on cardiovascular parameters were evaluated. HEX induced
endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 ± 4.1%;
potency [pD2] = 5.1 ± 0.1). Relaxation was attenuated by scavenging nitric oxide (ME =
44.9 ± 9.4% vs. 100.4 ± 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 ±
9.7% vs. 100.4 ± 4.1%). In addition, pD2 was decreased after non-selective blockade of
K
+ channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ±
0.1 vs. 5.1 ± 0.1). HEX increased NO levels in mesenteric arteries (33.2 ± 2.3 vs. 10.7 ±
0.2 au, p < 0.0001). Intravenous acute administration of HEX (1–20 mg/kg) induced
hypotension and bradycardia in normotensive and hypertensive rats. Furthermore,
starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the
HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ±
6 vs. 170 ± 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to
produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive
K
+ channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well
as produces antihypertensive effect in renovascular hypertensive rats.

A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones ... more A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones
with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains:
Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C.
tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of
the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration
(MIC) in the range of 64-512 μg mL-1. The compounds’ structures were fully confirmed and
characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic
resonance (NMR) and mass spectrometry (MS).

Abstract: Lung cancer is a disease with a high morbidity and high mortality rates. As a result, i... more Abstract: Lung cancer is a disease with a high morbidity and high mortality rates. As a result, it is
often associated with a significant amount of suffering and a general decrease in the quality of life.
Herbal drugs are recognized as one of attractive approaches for lung cancer therapy with little side
effects and are the main sources of new drugs. The aim of this review is to review the medicinal plants
with antitumor potential against lung cancer. The assays were conducted with humans and animals,
and Lewis lung carcinoma was the most used experimental model. Considering all the countries
covered in the study, India, China, Japan, and South Korea were the countries with the highest number
of species with antitumor activity on different experimental models. Of the 47 plants evaluated, 35
demonstrated antitumor activity. This review was based on NAPRALERT data bank, Web of Science
and Chemical Abstracts. This work shows that the natural products from plants continue being a rich
source of herbal medicines or biologically active compounds against cancer.

Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil ... more Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for
several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this
work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the
phytochemistry studies related to Bixa orellana L.Therefore, this work comprises a systematic review about the use of Bixa orellana
in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that
may be considered relevant for the future development of an innovative therapeutic agent.

Seven new compounds have been synthetized in satisfactory yields (51–78 %) through the treatment ... more Seven new compounds have been synthetized in satisfactory
yields (51–78 %) through the treatment of mesoionic
1,3-thiazolium-5-thiolate (4a–d) and 1,3,4-thiadiazolium-
5-thiolate (10a,b) with chloroacetic acid or methyl
iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate
(12). The structure of the title compounds was elucidated
by elemental analysis, IR, 1H and 13C NMR spectroscopy.
The newly synthesized compounds 5a, 6a, 11 and
12 were evaluated for their ex vivo spasmolytic potential
on four isolated smooth muscles (rat aorta and uterus,
guinea pig ileum and trachea) and compared with scopolamine.
Some of the compounds exhibited potent spasmolytic
activity equal to or stronger than scopolamine.

In the title compound, C11H10N2O3, which is a potential bioactive compound, the benzene and oxadi... more In the title compound, C11H10N2O3, which is a potential
bioactive compound, the benzene and oxadiazole rings are
approximately coplanar, with an inter-ring dihedral angle of
4.14 (2), while the ester plane is rotated out of the benzene
plane [dihedral angle = 82.69 (9)]. In the crystal, the
molecules form layers down the a axis with weak –
interactions between the oxadiazole and benzene rings
[minimum ring centroid separation = 3.7706 (14) A ° ]

The synthesis and complete 1 H and 13 C NMR and 19 F NMR spectra of 2-(ptrifluoromethylphenyl)-3-... more The synthesis and complete 1 H and 13 C NMR and 19 F NMR spectra of 2-(ptrifluoromethylphenyl)-3-methyl-4-(p-tolyl)-1,3-thiazolium-5-thiolate 2c and 2-(pchlorophenyl)-3-methyl-4-(p-isopropylphenyl)-1,3-thiazolium-5-thiolate 2d are described. Their structures are consistent with 1 H and 13 C NMR spectral assignments obtained by 2D NMR spectrometry. Structures were further confirmed by Elemental Analysis, IR, UV and Mass spectrometry and by X-ray diffraction.

Journal of Alloys and Compounds, 2010

The solids achieved in nanometric scale have been demanding scientific and technological interest... more The solids achieved in nanometric scale have been demanding scientific and technological interest due to the significant alterations in physical and chemical properties observed in such kind of materials, potentializing their technological applications. The nanocomplexes produced by lanthanide ions with the mesoionic compounds 2(4-clorophenil)-3-phenyl-1,3,4-thiadiazole-5-tiolate (M-1) were achieved in a powdered yellowed way. These compounds were characterized through X-ray diffraction, infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The X-ray diffractograms of the M-1 compound and of Er(M-1) 3 ·3H 2 O, Eu(M-1) 3 ·3H 2 O complexes, presented more than one phase and a crystalline structure. The disappearance and appearance of new peaks, as well as the variation on the intensity of the M-1 majoritary peaks as compared to the complexes' peaks can also be observed. The IR spectra indicate that the coordination of M-1 with the cations Eu +3 e Er +3 probably happens due to the sulfur exocyclic atom, where a considerable displacement in the carbon-sulfur (C-S)-ligation can be perceived. Comparing the DSC curves of the M-1, Er(M-1) 3 ·3H 2 O and Eu(M-1) 3 ·3H 2 O, a displacement of the complexes peaks in relation to M-1 can be observed, suggesting the achievement of new specimens. Thus, it can be concluded that the formation of two new organic nanocomplexes with crystalline characteristics which may be used as a pharmacy, is quite evident.

Journal of Thermal Analysis and Calorimetry, 2009

The mesoionic compounds are pentagonal heterocyclic betaines with their potential use mainly in t... more The mesoionic compounds are pentagonal heterocyclic betaines with their potential use mainly in the pharmacology field due to the diversity of their biological activities. Their exceptional electric properties lead the compounds to be investigated in the field such as the nonlinear optical devices. In this study, five mesoionic compounds of the 1,3-thiazole-5-thiolate system had been synthesized from amino acids derived from glycine through 1,3-dipolar cycloaddition/cycloreversion reaction. The compounds were characterized by the use of infrared spectrometry, thermogravimetry and differential scanning calorimetry techniques. Thermal stability of each structure was determined and characterized by the kinetic study of the thermal decomposition by non-isothermal thermogravimetry. The DSC curves for MI-1, MI-2, MI-3, MI-4, and MI-5 demonstrated their fusion and subsequent decomposition with the exception of MI-3, which presented only decomposition stages. The kinetic models that better described the thermal decomposition mechanism of the mesoionic compounds achieved by the non-isothermal methods were R1, R2 and R3 (based on the geometric models).

Zeitschrift für Naturforschung C, 2007

Crude ethanolic extract, lignoid fraction and the purified compound yangambin were obtained from ... more Crude ethanolic extract, lignoid fraction and the purified compound yangambin were obtained from Ocotea duckei (Lauraceae) and their antileishmanial activity was tested against promastigote forms of Leishmania chagasi and Leishmania amazonensis cultivated in Schneider medium, supplemented with 20% of fetal bovine serum. All substances presented antileishmanial activity with IC50 values of 135.7 μg/mL for the crude ethanolic extract, 26.5 μg/mL for the lignoid fraction and 49.0 μg/mL for yangambin on L. chagasi. For L. amazonensis the IC50 values were 143.7 μg/mL, 48.2 μg/mL and 64.9 μg/mL for the crude ethanolic extract, the lignoid fraction, and the purified compound yangambin, respectively. The crude ethanolic extract, lignoid fraction, and yangambin caused an inhibition higher than Glucantime“, a reference drug used for the treatment of leishmaniasis.

Acta pharmaceutica (Zagreb, Croatia), 2014

Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment ... more Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4-thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the title compounds was elucidated by elemental analysis, IR, (1)H and (13)C NMR spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated for their ex vivo spasmolytic potential on four isolated smooth muscles (rat aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine. Some of the compounds exhibited potent spasmolytic activity equal to or stronger than scopolamine.

J. Phys. Chem. C , 2018

The first hyperpolarizabilities of the mesoionic compounds (MICs) 2-(4-chlorophenyl)-3-methyl-4-p... more The first hyperpolarizabilities of the mesoionic compounds (MICs) 2-(4-chlorophenyl)-3-methyl-4-phenyl-1,3-thiazolium-5-thiolate (MIC-1), 2-(4-chlorophenyl)-3-methyl-4-(4-methylphenyl)-1,3-thiazolium-5-thiolate (MIC-2), and (2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1,3-thiazolium-5-thiolate) (MIC-3), dissolved in dimethyl sulfoxide (DMSO), are reported here for the first time to our knowledge. Hyper-Rayleigh scattering experiments were performed with an excitation source operating at λ = 1180 nm (ω = 8475 cm −1). The measured hyperpolarizability, β(2ω), was used to calculate the static hyperpolarizability, β(0), by applying the classical two-level model. The values obtained for β(0) were 10.1 × 10 −30 esu (MIC-1), 8.7 × 10 −30 esu (MIC-2), and 10.4 × 10 −30 esu (MIC-3) which are smaller than previous theoretical predictions that did not consider features related to the liquid phase. ■ INTRODUCTION Recent developments of nonlinear (NL) optical materials are concerned with the design of new systems with enhanced second-and third-order optical properties aiming their uses in optoelectronic devices, 1,2 all-optical limiters, 3 and THz imaging and spectroscopy, 4 among other applications. Important works have been reported with focus on the exploitation of new organic molecules because they present large NL optical coefficients, fast response times, straightforward synthesis, and processability. In particular, molecules with electronic push−pull systems, which give rise to π-electrons delocalization, present large optical hyperpolarizabilities and fast response for nonresonant excitation. 5−12 Organic molecules formed by push−pull systems have three components; an electro-acceptor group (R A), an electron-donor group (R D) and a π-conjugated spacer to link the R A and R D. 9,10 The goal is to engineer the components in order to maximize the optical hyperpolarizabilities. Among the push−pull organic systems known, the mesoionic compounds (MICs) deserve special attention because of their remarkable physical and chemical properties that enable applications as antioxidant, 13 anti-inflammatory, 14 antibacterial, 15 and antitumor sumstances, 16 as well as the large NL optical susceptibility as already proposed 17−19 and experimentally demonstrated. 20−22 Indeed, the MICs' properties point to NL biophotonics as a possible avenue for future applications. MICs are planar five-membered heterocyclic betaines, with at least one side-chain whose atom is also in the ring plane where the positive and negative charges are separated and delocalized within a π-electrons system that originate permanent electric dipole moments of ≈5 D. The region, which includes the side chain atom, is associated with highest occupied molecular orbital (HOMO) and a negative π-charge, while the other is associated with lowest unoccupied molecular orbital (LUMO) and a positive π-charge. 18 The molecules are neutral, they present π-electron delocalization, and they are composed of resonant (mesomeric) structures. In previous theoretical studies the potential of MICs for NL optics was considered on the basis of their high hyper-polarizability values, their stability and the possibility of improving their optical response by manipulation of their chemical structure. 17,19 The studies revealed that certain MICs present relatively high third-order NL optical response in the visible and near-infrared regions that were verified in experiments with pulsed lasers operating in various temporal regimes. For example, two-photon absorption cross sections in

Biomedicine & Pharmacotherapy, 2020

Structural diversity characterizes natural products as prototypes for design of lead compounds. T... more Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and mi-cronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC 50 (lethal concentration 50%) higher than 100 μg/mL. On the acute toxicity assay in mice, LD 50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1β, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.

A B S T R A C T Rationale: Development and progression of cardiovascular diseases, including hype... more A B S T R A C T Rationale: Development and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance. In this study, we evaluated NO release capability and cardiovascular effects of the newly synthesized organic nitrate 1, 3-bis (hexyloxy) propan-2-yl nitrate (NDHP). Methods: A combination of in vitro and in vivo approaches was utilized to assess acute effects of NDHP on NO release, vascular reactivity and blood pressure. The therapeutic value of chronic NDHP treatment was assessed in an experimental model of angiotensin II-induced hypertension in combination with NOS inhibition. Results: NDHP mediates NO formation in both cell-free system and small resistance arteries, a process which is catalyzed by xanthine oxidoreductase. NDHP-induced vasorelaxation is endothelium independent and mediated by NO release and modulation of potassium channels. Reduction of blood pressure following acute intravenous infusion of NDHP was more pronounced in hypertensive rats (two-kidney-one-clip model) than in normotensive sham-operated rats. Toxicological tests did not reveal any harmful effects following treatment with high doses of NDHP. Finally, chronic treatment with NDHP significantly attenuated the development of hypertension and endothelial dysfunction in rats with chronic NOS inhibition and angiotensin II infusion. Conclusion: Acute treatment with the novel organic nitrate NDHP increases NO formation, which is associated with vasorelaxation and a significant reduction of blood pressure in hypertensive animals. Chronic NDHP treatment attenuates the progression of hypertension and endothelial dysfunction, suggesting a potential for therapeutic applications in cardiovascular disease.

Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were f... more Nine new compounds derived from selenoglycolic acid were synthesized, and their structures were fully characterized by elemental analysis, infrared (IR), 1 H and 13 C nuclear magnetic resonance (NMR). The compounds were evaluated in an in silico study and showed strong to moderate antibacterial activity against several strains of Staphylococcus aureus. In particular, three compounds exhibited excellent antibacterial activity, with minimum inhibitory concentrations (MICs) between 16 and 64 μg mL-1. Furthermore, two of the nine compounds showed antifungal activity, with MIC of 1024 and 512 μg mL-1. In silico studies of the parameters of Lipinski's rule of five indicate that these compounds have potential to be new drug candidates.

A B S T R A C T In this report, we describe the synthesis and characterization of 1,3-bis(hexylox... more A B S T R A C T In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.

Journal of Thermal Analysis and Calorimetry, 2005

Page 1. Introduction The tropical shrub Urucum internationally known as annatto (Bixa orellana L.... more Page 1. Introduction The tropical shrub Urucum internationally known as annatto (Bixa orellana L.) is a small tree with predom-inant occurrence in the South American regions (par-ticularly in Brazil). Bixin is the major component ...

We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate ... more We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane
Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic
treatment with HEX on cardiovascular parameters were evaluated. HEX induced
endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 ± 4.1%;
potency [pD2] = 5.1 ± 0.1). Relaxation was attenuated by scavenging nitric oxide (ME =
44.9 ± 9.4% vs. 100.4 ± 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 ±
9.7% vs. 100.4 ± 4.1%). In addition, pD2 was decreased after non-selective blockade of
K
+ channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ±
0.1 vs. 5.1 ± 0.1). HEX increased NO levels in mesenteric arteries (33.2 ± 2.3 vs. 10.7 ±
0.2 au, p < 0.0001). Intravenous acute administration of HEX (1–20 mg/kg) induced
hypotension and bradycardia in normotensive and hypertensive rats. Furthermore,
starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the
HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ±
6 vs. 170 ± 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to
produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive
K
+ channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well
as produces antihypertensive effect in renovascular hypertensive rats.

A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones ... more A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones
with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains:
Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C.
tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of
the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration
(MIC) in the range of 64-512 μg mL-1. The compounds’ structures were fully confirmed and
characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic
resonance (NMR) and mass spectrometry (MS).

Abstract: Lung cancer is a disease with a high morbidity and high mortality rates. As a result, i... more Abstract: Lung cancer is a disease with a high morbidity and high mortality rates. As a result, it is
often associated with a significant amount of suffering and a general decrease in the quality of life.
Herbal drugs are recognized as one of attractive approaches for lung cancer therapy with little side
effects and are the main sources of new drugs. The aim of this review is to review the medicinal plants
with antitumor potential against lung cancer. The assays were conducted with humans and animals,
and Lewis lung carcinoma was the most used experimental model. Considering all the countries
covered in the study, India, China, Japan, and South Korea were the countries with the highest number
of species with antitumor activity on different experimental models. Of the 47 plants evaluated, 35
demonstrated antitumor activity. This review was based on NAPRALERT data bank, Web of Science
and Chemical Abstracts. This work shows that the natural products from plants continue being a rich
source of herbal medicines or biologically active compounds against cancer.

Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil ... more Bixa orellana L., popularly known as “urucum,” has been used by indigenous communities in Brazil and other tropical countries for
several biological applications, which indicates its potential use as an active ingredient in pharmaceutical products. The aim of this
work was to report the main evidence found in the literature, concerning the ethnopharmacology, the biological activity, and the
phytochemistry studies related to Bixa orellana L.Therefore, this work comprises a systematic review about the use of Bixa orellana
in the American continent and analysis of the data collected. This study shows the well-characterized pharmacological actions that
may be considered relevant for the future development of an innovative therapeutic agent.

Seven new compounds have been synthetized in satisfactory yields (51–78 %) through the treatment ... more Seven new compounds have been synthetized in satisfactory
yields (51–78 %) through the treatment of mesoionic
1,3-thiazolium-5-thiolate (4a–d) and 1,3,4-thiadiazolium-
5-thiolate (10a,b) with chloroacetic acid or methyl
iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate
(12). The structure of the title compounds was elucidated
by elemental analysis, IR, 1H and 13C NMR spectroscopy.
The newly synthesized compounds 5a, 6a, 11 and
12 were evaluated for their ex vivo spasmolytic potential
on four isolated smooth muscles (rat aorta and uterus,
guinea pig ileum and trachea) and compared with scopolamine.
Some of the compounds exhibited potent spasmolytic
activity equal to or stronger than scopolamine.

In the title compound, C11H10N2O3, which is a potential bioactive compound, the benzene and oxadi... more In the title compound, C11H10N2O3, which is a potential
bioactive compound, the benzene and oxadiazole rings are
approximately coplanar, with an inter-ring dihedral angle of
4.14 (2), while the ester plane is rotated out of the benzene
plane [dihedral angle = 82.69 (9)]. In the crystal, the
molecules form layers down the a axis with weak –
interactions between the oxadiazole and benzene rings
[minimum ring centroid separation = 3.7706 (14) A ° ]

The synthesis and complete 1 H and 13 C NMR and 19 F NMR spectra of 2-(ptrifluoromethylphenyl)-3-... more The synthesis and complete 1 H and 13 C NMR and 19 F NMR spectra of 2-(ptrifluoromethylphenyl)-3-methyl-4-(p-tolyl)-1,3-thiazolium-5-thiolate 2c and 2-(pchlorophenyl)-3-methyl-4-(p-isopropylphenyl)-1,3-thiazolium-5-thiolate 2d are described. Their structures are consistent with 1 H and 13 C NMR spectral assignments obtained by 2D NMR spectrometry. Structures were further confirmed by Elemental Analysis, IR, UV and Mass spectrometry and by X-ray diffraction.

Journal of Alloys and Compounds, 2010

The solids achieved in nanometric scale have been demanding scientific and technological interest... more The solids achieved in nanometric scale have been demanding scientific and technological interest due to the significant alterations in physical and chemical properties observed in such kind of materials, potentializing their technological applications. The nanocomplexes produced by lanthanide ions with the mesoionic compounds 2(4-clorophenil)-3-phenyl-1,3,4-thiadiazole-5-tiolate (M-1) were achieved in a powdered yellowed way. These compounds were characterized through X-ray diffraction, infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The X-ray diffractograms of the M-1 compound and of Er(M-1) 3 ·3H 2 O, Eu(M-1) 3 ·3H 2 O complexes, presented more than one phase and a crystalline structure. The disappearance and appearance of new peaks, as well as the variation on the intensity of the M-1 majoritary peaks as compared to the complexes' peaks can also be observed. The IR spectra indicate that the coordination of M-1 with the cations Eu +3 e Er +3 probably happens due to the sulfur exocyclic atom, where a considerable displacement in the carbon-sulfur (C-S)-ligation can be perceived. Comparing the DSC curves of the M-1, Er(M-1) 3 ·3H 2 O and Eu(M-1) 3 ·3H 2 O, a displacement of the complexes peaks in relation to M-1 can be observed, suggesting the achievement of new specimens. Thus, it can be concluded that the formation of two new organic nanocomplexes with crystalline characteristics which may be used as a pharmacy, is quite evident.

Journal of Thermal Analysis and Calorimetry, 2009

The mesoionic compounds are pentagonal heterocyclic betaines with their potential use mainly in t... more The mesoionic compounds are pentagonal heterocyclic betaines with their potential use mainly in the pharmacology field due to the diversity of their biological activities. Their exceptional electric properties lead the compounds to be investigated in the field such as the nonlinear optical devices. In this study, five mesoionic compounds of the 1,3-thiazole-5-thiolate system had been synthesized from amino acids derived from glycine through 1,3-dipolar cycloaddition/cycloreversion reaction. The compounds were characterized by the use of infrared spectrometry, thermogravimetry and differential scanning calorimetry techniques. Thermal stability of each structure was determined and characterized by the kinetic study of the thermal decomposition by non-isothermal thermogravimetry. The DSC curves for MI-1, MI-2, MI-3, MI-4, and MI-5 demonstrated their fusion and subsequent decomposition with the exception of MI-3, which presented only decomposition stages. The kinetic models that better described the thermal decomposition mechanism of the mesoionic compounds achieved by the non-isothermal methods were R1, R2 and R3 (based on the geometric models).