magnified image This review intends to explore synthetic methodologies for the preparation of 2H‐... more magnified image This review intends to explore synthetic methodologies for the preparation of 2H‐chromenes and their analog chromanes through ortho‐quinone methide (o‐QM) intermediates associated with inter and intramolecular hetero‐Diels‐Alder and electrocyclization reactions. J. Heterocyclic Chem., (2009).
Objective The present study aimed to investigate five triazole compounds as P2X7R inhibitors and ... more Objective The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo. Material The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12. Treatment We administered 500 ng/kg triazole analogs in vivo, (1-10 µM) in vitro, and 1000 mg/kg for toxicological assays. Methods For this, we used in vitro experiments, such as platelet aggregation, in vivo experiments of paw edema and peritonitis in mice, and in silico experiments. Results The tested substances 5e, 8h, 9i, 11, and 12 produced a significant reduction in paw edema. Molecules 5e, 8h, 9i, 11, and 12 inhibited carrageenan-induced peritonitis. Substances 5e, 8h, 9i, 11, and 12 showed an anticoagulant effect, and 5e at a concentration of 10 µM acted as a procoagulant. All derivatives, except for 11, had pharmacokinetic, physicochemical, and toxicological properties suitable for substances that are candidates for new drugs. In addition, the ADMET risk assessment shows that derivatives 8h, 11, 5e, and 9i have high pharmacological potential. Finally, docking tests indicated that the derivatives have binding energies comparable to the reference antagonist with a competitive inhibition profile. Conclusions Together, the results indicate that the molecules tested as antagonist drugs of P2X7R had anti-inflammatory action against the acute inflammatory response.
Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 recepto... more Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 receptor (P2X7R) inhibitors. P2X7R inhibition in vitro was evaluated in mouse peritoneal macrophages, HEK-293 cells transfected with hP2X7R (dye uptake assay), and THP-1 cells (IL-1β release assay). The 1-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrazol-5-amine derivatives 9b, 9c, and 9f, and 2-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(4-fluorophenyl)-1,3,4-thiadiazole (11c) showed inhibitory effects with IC 50 values ranging from 16 to 122 nM for reduced P2X7R-mediated dye uptake and 20 to 300 nM for IL-1β release. In addition, the in vitro ADMET profile of the four most potent derivatives was determined to be in acceptable ranges concerning metabolic stability and cytotoxicity. Molecular docking and molecular dynamics simulation studies of the molecular complexes human P2X7R/9f and murine P2X7R/9f indicated the putative intermolecular interactions. Compound 9f showed affinity mainly for the Arg268, Lys377, and Asn266 residues. These results suggest that 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs may be promising novel P2X7R inhibitors with therapeutic potential.
Current Topics in Medicinal Chemistry, Nov 1, 2013
The 1H-1,2,3-triazoles have been studied for many years as an important class of heterocyclic com... more The 1H-1,2,3-triazoles have been studied for many years as an important class of heterocyclic compounds and still attracting considerable attention due to their several application such as, organocatalyst, ionic liquid and broad range of biological activities, including several neglected diseases as tuberculosis. This review emphasizes the recent advances of these triazoles and their perspective in the development of new bioactive chemical entities against tuberculosis.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Natural and synthetic waxes are complex mixtures of chemical compounds that represent an importan... more Natural and synthetic waxes are complex mixtures of chemical compounds that represent an important class of organic compounds responsible for a large international market. The demand for new applications of waxes has been increasing and all projections indicate that there will be an increase on average of 6% until 2027, where it is already speculated that the substitutes for synthetic and petroleum waxes are natural waxes. The ability of new and growing applications to adapt to non-petroleum types of wax will set the stage for the future and the supply and demand of natural waxes as they grow under the influence of social norms, culture, beliefs and styles of life. The 2019 global wax emulsion market is estimated at US$ 1.6 billion and is expected to grow to US$ 2.0 billion in 2024, with a compound annual growth rate (CAGR) of 4.9% from 2019 to 2024. Thus, this article intends to describe the main natural waxes and some of their applications.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined w... more Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with pa...
The death of professor Rolf Huisgen (1920-2020) was announced on March 26th 2020, in the midst of... more The death of professor Rolf Huisgen (1920-2020) was announced on March 26th 2020, in the midst of the COVID-19 pandemic. Professor Huisgen was professor emeritus at the University of Munich in Germany, and studied in detail the mechanism of the 1,3-dipolar cycloaddition reaction, significantly expanding its scope. Even though he did not discover this reaction, it was through his studies that it became important in organic synthesis. Indeed, in honor of his work, the reaction became known as Huisgen’s cycloaddition and it has been consolidated as a useful method for the preparation of five-membered heterocyclic compounds. Considering these facts, in this review we provide an overview on the applications of 1,3-dipolar cycloaddition reactions, starting with the seminal examples in the field and further discussing the most recent applications.
... Review. Syntheses of chromenes and chromanes via o-quinone methide intermediates. Sabrina B. ... more ... Review. Syntheses of chromenes and chromanes via o-quinone methide intermediates. Sabrina B. Ferreira 1 ,; Fernando de C. da Silva 1,2 ,; Angelo C. Pinto 2 ,; Daniel TG Gonzaga 1 ,; Vitor F. Ferreira 1,*. Article first published online: 12 NOV 2009. DOI: 10.1002/jhet.232. ...
Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae fam... more Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were perf...
Plant extracts of Eugenia punicifolia (Kunth) DC., Myrtaceae, are used in Amazon region of Brazil... more Plant extracts of Eugenia punicifolia (Kunth) DC., Myrtaceae, are used in Amazon region of Brazil to treat diarrhea and stomach disturbances, and as hypoglycemic medicine. We have recently shown that an aqueous extract of E. punicifolia augmented cholinergic neurotransmission in a rat phrenic nerve-diaphragm preparation. In this study, we investigated the effects of an E. punicifolia dichloromethane extract (EPEX) in a neuronal model of cholinergic neurotransmission, the bovine adrenal chromaffin cell. EPEX augmented the release of catecholamine triggered by acetylcholine (ACh) pulses but did not enhance AChevoked inward currents, which were inhibited by 30%. Since EPEX did not cause a blockade of acetylcholinesterase or butyrylcholinesterase, it seems that EPEX is not directly activating the cholinergic system. EPEX also augmented K+-elicited secretion without enhancing the whole-cell inward calcium current. This novel and potent effect of EPEX in enhancing exocytosis might help to...
The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and ... more The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and consist of the demineralization of the tooth that occurs when the acid production overcomes the natural repair or if a problem occurs in the last one. In this work, we performed the synthesis of twenty-one 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles (8a-8k and 9a-9j), antibacterial evaluation against the S. mutans in vitro and the acute toxicity of the better ones in vivo. We observed strong inhibition results in the disc diffusion test ranging, the halos of inhibitions, from 18.66 (± 0.57) to 29 (± 2.64) mm, and good values in the minimum inhibitory concentration (5 to 50 μg), for the compounds 9e, 9h, 9i and 9j. Furthermore, they do not have a cytotoxic effect at the concentrations tested. Besides that, in the in vivo test, they show some slight alteration in the histopathological analyses and the biochemistry. Thus, we found four potential candidates to become instruments for t...
Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 recepto... more Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 receptor (P2X7R) inhibitors. P2X7R inhibition in vitro was evaluated in mouse peritoneal macrophages, HEK-293 cells transfected with hP2X7R (dye uptake assay), and THP-1 cells (IL-1β release assay). The 1-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrazol-5-amine derivatives 9b, 9c, and 9f, and 2-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(4-fluorophenyl)-1,3,4-thiadiazole (11c) showed inhibitory effects with IC50 values ranging from 16 to 122 nM for reduced P2X7R-mediated dye uptake and 20 to 300 nM for IL-1β release. In addition, the in vitro ADMET profile of the four most potent derivatives was determined to be in acceptable ranges concerning metabolic stability and cytotoxicity. Molecular docking and molecular dynamics simulation studies of the molecular complexes human P2X7R/9f and murine P2X7R/9f indicated the putative intermolecular interactions. Compound 9f showed affinity mainly for the Arg268, Lys377,...
Background: Resistance to antimicrobial agents is a major public health problem, being Staphyloco... more Background: Resistance to antimicrobial agents is a major public health problem, being Staphylococcus aureus prevalent in infections in hospital and community environments and, admittedly, related to biofilm formation in biotic and abiotic surfaces. Biofilms form a complex and structured community of microorganisms surrounded by an extracellular matrix adhering to each other and to a surface that gives them even more protection from and resistance against the action of antimicrobial agents, as well as against host defenses. Methods: Aiming to control and solve these problems, our study sought to evaluate the action of 1,2,3- triazoles against a Staphylococcus aureus isolate in planktonic and in the biofilm form, evaluating the activity of this triazole through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. We have also performed cytotoxic evaluation and Scanning Electron Microscopy (SEM) of the biofilms under the treatment of the compound....
The search for new compounds with antimalarial activity is urgent, as resistance to ones in the c... more The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite Plasmodium falciparum in a culture of fifty-four triazole compounds derived from 1H-and 2H-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC50 values ranging from 2.80 µM (9) to 29.27 µM (21). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for P. falciparum G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC50 values for the knockout strain. The cyto...
Zika virus (ZIKV) is a mosquito-borne pathogen which is a current global public health concern. T... more Zika virus (ZIKV) is a mosquito-borne pathogen which is a current global public health concern. There are currently no approved vaccines or antivirals against ZIKV infection. Taking into account that naphthoquinones have shown promising antiviral activity, the aim of this study was to describe the screening of two bis-naphthoquinones series against ZIKV. Twenty seven compounds were evaluated against ZIKV using Vero cells. The findings showed that among the compounds analyzed four were promising. Compound 3,3'-((2-nitrophenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione) containing the nitro group at the ortho position showed the best selectivity index, followed by compound 3,3'-(4-chlorophenylmethylene)bis(naphthalene-1,2,4-triyl triacetate) with the chlorophenylmethylene radical. These results demonstrate that these bis-naphthoquinones are largely effective in inhibiting the replication of ZIKV.
Background: Antibacterial resistance is a serious public health problem infecting millions in glo... more Background: Antibacterial resistance is a serious public health problem infecting millions in global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, it is an urgent need for new therapeutic options against these strains. Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains. Method: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays. Result: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2-hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluatio...
Carbenes and NHCs play an important role in porphyrin chemistry and several synthetically useful ... more Carbenes and NHCs play an important role in porphyrin chemistry and several synthetically useful transformations leading to the preparation of new porphyrin derivatives have been developed. This short review presents an overview covering the literature from 2007–2017, on the role of these transient species in the functionalization of porphyrin macrocycles.
Current topics in medicinal chemistry, Jan 21, 2018
Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by ... more Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by using the tools of medicinal chemistry. The 1,2,4-triazole rings are part of an extensive family of drugs that are in use in the pharmaceutical market. More recently 1,2,3-triazole rings have begun to arouse great interest of scientists and therefore, many researches have been developed seeking the synthesis of new substances and their possible biological activities. A number of articles have been published by us and others highlighting the synthetic and biological aspects of 1,2,3-triazoles. The growth of new substances of this class was largely due to the simple and selective synthetic method of 1,2,3-triazole ring developed by Sharpless et al. However, some 1,2,3-triazole cannot be synthesized by this method. This review focuses on other synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibi...
magnified image This review intends to explore synthetic methodologies for the preparation of 2H‐... more magnified image This review intends to explore synthetic methodologies for the preparation of 2H‐chromenes and their analog chromanes through ortho‐quinone methide (o‐QM) intermediates associated with inter and intramolecular hetero‐Diels‐Alder and electrocyclization reactions. J. Heterocyclic Chem., (2009).
Objective The present study aimed to investigate five triazole compounds as P2X7R inhibitors and ... more Objective The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo. Material The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12. Treatment We administered 500 ng/kg triazole analogs in vivo, (1-10 µM) in vitro, and 1000 mg/kg for toxicological assays. Methods For this, we used in vitro experiments, such as platelet aggregation, in vivo experiments of paw edema and peritonitis in mice, and in silico experiments. Results The tested substances 5e, 8h, 9i, 11, and 12 produced a significant reduction in paw edema. Molecules 5e, 8h, 9i, 11, and 12 inhibited carrageenan-induced peritonitis. Substances 5e, 8h, 9i, 11, and 12 showed an anticoagulant effect, and 5e at a concentration of 10 µM acted as a procoagulant. All derivatives, except for 11, had pharmacokinetic, physicochemical, and toxicological properties suitable for substances that are candidates for new drugs. In addition, the ADMET risk assessment shows that derivatives 8h, 11, 5e, and 9i have high pharmacological potential. Finally, docking tests indicated that the derivatives have binding energies comparable to the reference antagonist with a competitive inhibition profile. Conclusions Together, the results indicate that the molecules tested as antagonist drugs of P2X7R had anti-inflammatory action against the acute inflammatory response.
Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 recepto... more Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 receptor (P2X7R) inhibitors. P2X7R inhibition in vitro was evaluated in mouse peritoneal macrophages, HEK-293 cells transfected with hP2X7R (dye uptake assay), and THP-1 cells (IL-1β release assay). The 1-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrazol-5-amine derivatives 9b, 9c, and 9f, and 2-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(4-fluorophenyl)-1,3,4-thiadiazole (11c) showed inhibitory effects with IC 50 values ranging from 16 to 122 nM for reduced P2X7R-mediated dye uptake and 20 to 300 nM for IL-1β release. In addition, the in vitro ADMET profile of the four most potent derivatives was determined to be in acceptable ranges concerning metabolic stability and cytotoxicity. Molecular docking and molecular dynamics simulation studies of the molecular complexes human P2X7R/9f and murine P2X7R/9f indicated the putative intermolecular interactions. Compound 9f showed affinity mainly for the Arg268, Lys377, and Asn266 residues. These results suggest that 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs may be promising novel P2X7R inhibitors with therapeutic potential.
Current Topics in Medicinal Chemistry, Nov 1, 2013
The 1H-1,2,3-triazoles have been studied for many years as an important class of heterocyclic com... more The 1H-1,2,3-triazoles have been studied for many years as an important class of heterocyclic compounds and still attracting considerable attention due to their several application such as, organocatalyst, ionic liquid and broad range of biological activities, including several neglected diseases as tuberculosis. This review emphasizes the recent advances of these triazoles and their perspective in the development of new bioactive chemical entities against tuberculosis.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Natural and synthetic waxes are complex mixtures of chemical compounds that represent an importan... more Natural and synthetic waxes are complex mixtures of chemical compounds that represent an important class of organic compounds responsible for a large international market. The demand for new applications of waxes has been increasing and all projections indicate that there will be an increase on average of 6% until 2027, where it is already speculated that the substitutes for synthetic and petroleum waxes are natural waxes. The ability of new and growing applications to adapt to non-petroleum types of wax will set the stage for the future and the supply and demand of natural waxes as they grow under the influence of social norms, culture, beliefs and styles of life. The 2019 global wax emulsion market is estimated at US$ 1.6 billion and is expected to grow to US$ 2.0 billion in 2024, with a compound annual growth rate (CAGR) of 4.9% from 2019 to 2024. Thus, this article intends to describe the main natural waxes and some of their applications.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined w... more Recently, the well-known geographically wide distribution of sporotrichosis in Brazil, combined with the difficulties of effective domestic feline treatment, has emphasized the pressing need for new therapeutic alternatives. This work considers a range of synthetic derivatives as potential antifungals against Sporothrix brasiliensis isolated from cats from the hyperendemic Brazilian region. Six S. brasiliensis isolates from the sporotrichotic lesions of itraconazole responsive or non-responsive domestic cats were studied. The minimum inhibitory concentrations (MICs) of three novel hydrazone derivatives and eleven novel quinone derivatives were determined using the broth microdilution method (M38-A2). In silico tests were also used to predict the pharmacological profile and toxicity parameters of these synthetic derivatives. MICs and MFCs ranged from 1 to >128 µg/mL. The ADMET computational analysis failed to detect toxicity while a good pharmacological predictive profile, with pa...
The death of professor Rolf Huisgen (1920-2020) was announced on March 26th 2020, in the midst of... more The death of professor Rolf Huisgen (1920-2020) was announced on March 26th 2020, in the midst of the COVID-19 pandemic. Professor Huisgen was professor emeritus at the University of Munich in Germany, and studied in detail the mechanism of the 1,3-dipolar cycloaddition reaction, significantly expanding its scope. Even though he did not discover this reaction, it was through his studies that it became important in organic synthesis. Indeed, in honor of his work, the reaction became known as Huisgen’s cycloaddition and it has been consolidated as a useful method for the preparation of five-membered heterocyclic compounds. Considering these facts, in this review we provide an overview on the applications of 1,3-dipolar cycloaddition reactions, starting with the seminal examples in the field and further discussing the most recent applications.
... Review. Syntheses of chromenes and chromanes via o-quinone methide intermediates. Sabrina B. ... more ... Review. Syntheses of chromenes and chromanes via o-quinone methide intermediates. Sabrina B. Ferreira 1 ,; Fernando de C. da Silva 1,2 ,; Angelo C. Pinto 2 ,; Daniel TG Gonzaga 1 ,; Vitor F. Ferreira 1,*. Article first published online: 12 NOV 2009. DOI: 10.1002/jhet.232. ...
Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae fam... more Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were perf...
Plant extracts of Eugenia punicifolia (Kunth) DC., Myrtaceae, are used in Amazon region of Brazil... more Plant extracts of Eugenia punicifolia (Kunth) DC., Myrtaceae, are used in Amazon region of Brazil to treat diarrhea and stomach disturbances, and as hypoglycemic medicine. We have recently shown that an aqueous extract of E. punicifolia augmented cholinergic neurotransmission in a rat phrenic nerve-diaphragm preparation. In this study, we investigated the effects of an E. punicifolia dichloromethane extract (EPEX) in a neuronal model of cholinergic neurotransmission, the bovine adrenal chromaffin cell. EPEX augmented the release of catecholamine triggered by acetylcholine (ACh) pulses but did not enhance AChevoked inward currents, which were inhibited by 30%. Since EPEX did not cause a blockade of acetylcholinesterase or butyrylcholinesterase, it seems that EPEX is not directly activating the cholinergic system. EPEX also augmented K+-elicited secretion without enhancing the whole-cell inward calcium current. This novel and potent effect of EPEX in enhancing exocytosis might help to...
The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and ... more The cariogenic processes are mainly caused by the bacterium Streptococcus mutans (S. mutans) and consist of the demineralization of the tooth that occurs when the acid production overcomes the natural repair or if a problem occurs in the last one. In this work, we performed the synthesis of twenty-one 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles (8a-8k and 9a-9j), antibacterial evaluation against the S. mutans in vitro and the acute toxicity of the better ones in vivo. We observed strong inhibition results in the disc diffusion test ranging, the halos of inhibitions, from 18.66 (± 0.57) to 29 (± 2.64) mm, and good values in the minimum inhibitory concentration (5 to 50 μg), for the compounds 9e, 9h, 9i and 9j. Furthermore, they do not have a cytotoxic effect at the concentrations tested. Besides that, in the in vivo test, they show some slight alteration in the histopathological analyses and the biochemistry. Thus, we found four potential candidates to become instruments for t...
Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 recepto... more Twenty new 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole analogs were synthetized to develop P2X7 receptor (P2X7R) inhibitors. P2X7R inhibition in vitro was evaluated in mouse peritoneal macrophages, HEK-293 cells transfected with hP2X7R (dye uptake assay), and THP-1 cells (IL-1β release assay). The 1-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrazol-5-amine derivatives 9b, 9c, and 9f, and 2-(3,5-dimethyl-1H-pyrazol-1-yl)-5-(4-fluorophenyl)-1,3,4-thiadiazole (11c) showed inhibitory effects with IC50 values ranging from 16 to 122 nM for reduced P2X7R-mediated dye uptake and 20 to 300 nM for IL-1β release. In addition, the in vitro ADMET profile of the four most potent derivatives was determined to be in acceptable ranges concerning metabolic stability and cytotoxicity. Molecular docking and molecular dynamics simulation studies of the molecular complexes human P2X7R/9f and murine P2X7R/9f indicated the putative intermolecular interactions. Compound 9f showed affinity mainly for the Arg268, Lys377,...
Background: Resistance to antimicrobial agents is a major public health problem, being Staphyloco... more Background: Resistance to antimicrobial agents is a major public health problem, being Staphylococcus aureus prevalent in infections in hospital and community environments and, admittedly, related to biofilm formation in biotic and abiotic surfaces. Biofilms form a complex and structured community of microorganisms surrounded by an extracellular matrix adhering to each other and to a surface that gives them even more protection from and resistance against the action of antimicrobial agents, as well as against host defenses. Methods: Aiming to control and solve these problems, our study sought to evaluate the action of 1,2,3- triazoles against a Staphylococcus aureus isolate in planktonic and in the biofilm form, evaluating the activity of this triazole through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. We have also performed cytotoxic evaluation and Scanning Electron Microscopy (SEM) of the biofilms under the treatment of the compound....
The search for new compounds with antimalarial activity is urgent, as resistance to ones in the c... more The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite Plasmodium falciparum in a culture of fifty-four triazole compounds derived from 1H-and 2H-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC50 values ranging from 2.80 µM (9) to 29.27 µM (21). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for P. falciparum G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC50 values for the knockout strain. The cyto...
Zika virus (ZIKV) is a mosquito-borne pathogen which is a current global public health concern. T... more Zika virus (ZIKV) is a mosquito-borne pathogen which is a current global public health concern. There are currently no approved vaccines or antivirals against ZIKV infection. Taking into account that naphthoquinones have shown promising antiviral activity, the aim of this study was to describe the screening of two bis-naphthoquinones series against ZIKV. Twenty seven compounds were evaluated against ZIKV using Vero cells. The findings showed that among the compounds analyzed four were promising. Compound 3,3'-((2-nitrophenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione) containing the nitro group at the ortho position showed the best selectivity index, followed by compound 3,3'-(4-chlorophenylmethylene)bis(naphthalene-1,2,4-triyl triacetate) with the chlorophenylmethylene radical. These results demonstrate that these bis-naphthoquinones are largely effective in inhibiting the replication of ZIKV.
Background: Antibacterial resistance is a serious public health problem infecting millions in glo... more Background: Antibacterial resistance is a serious public health problem infecting millions in global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, it is an urgent need for new therapeutic options against these strains. Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains. Method: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays. Result: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2-hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluatio...
Carbenes and NHCs play an important role in porphyrin chemistry and several synthetically useful ... more Carbenes and NHCs play an important role in porphyrin chemistry and several synthetically useful transformations leading to the preparation of new porphyrin derivatives have been developed. This short review presents an overview covering the literature from 2007–2017, on the role of these transient species in the functionalization of porphyrin macrocycles.
Current topics in medicinal chemistry, Jan 21, 2018
Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by ... more Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by using the tools of medicinal chemistry. The 1,2,4-triazole rings are part of an extensive family of drugs that are in use in the pharmaceutical market. More recently 1,2,3-triazole rings have begun to arouse great interest of scientists and therefore, many researches have been developed seeking the synthesis of new substances and their possible biological activities. A number of articles have been published by us and others highlighting the synthetic and biological aspects of 1,2,3-triazoles. The growth of new substances of this class was largely due to the simple and selective synthetic method of 1,2,3-triazole ring developed by Sharpless et al. However, some 1,2,3-triazole cannot be synthesized by this method. This review focuses on other synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibi...
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Papers by Daniel Gonzaga