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Papers by Rodrigo A. de Souza
Química Nova
SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY EVALUATION OF CYCLOPALLADATED COMPOUNDS CONTAI... more SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY EVALUATION OF CYCLOPALLADATED COMPOUNDS CONTAINING ORTHOMETALLATED BENZALDEHYDEOXIME AND ETHYLENETHIOUREA AS LIGANDS. The halidebridge cleavage reaction of the [Pd(C 2 ,N-bzox)(µ-Cl)] 2 compound (bzox = benzaldehydeoxime) with ethylenethiourea (L) in the 1:2 molar ratio at room temperature yielded the cyclopalladated compound [Pd(C 2 ,N-bzox)(Cl)(L)] (1) whose replacement of the halide group by the addition of suitable salts afforded compounds of general formulae [Pd(C 2 ,N-bzox)(X)(L)] {X = Br-(2), I-(3)}. All compounds were characterized by melting point, elemental analyses, infrared and 1 Hand 13 C{ 1 H}-NMR spectroscopies revealing the complexes formation with the oxime coordinated to Pd(II) as C,N-chelating and the ethylenethiourea as a monodentate ligand via the sulfur atom. The cytotoxicity of cyclopalladated compounds has been evaluated in vitro against murine mammary tumor cell (LM3) showing cytotoxic activity similar to cisplatin.
Revista Brasileira de Farmacognosia, 2014
The use of indigenous or remote popular knowledge to identify new drugs against diseases or infec... more The use of indigenous or remote popular knowledge to identify new drugs against diseases or infections is a well-known approach in medicine. The inhabitants of coastal regions are known to prepare algae extracts for the treatment of disorders and ailments such as wounds, fever and stomach aches, as for the prevention of arrhythmia. Recent trends in drug research from natural sources have indicated that marine algae are a promising source of novel biochemically active compounds, especially with antiprotozoal activity. Algae survive in a competitive environment and, therefore, developed defense strategies that have resulted in a significant level of chemical structural diversity in various metabolic pathways. The exploration of these organisms for pharmaceutical and medical purposes has provided important chemical candidates for the discovery of new agents against neglected tropical diseases, stimulating the use of sophisticated physical techniques. This current review describes the main substances biosynthesized by benthic marine algae with activity against Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei; the causative agents of leishmaniasis, Chagas disease and African trypanosomiasis, respectively. Emphasis is given to secondary metabolites and crude extracts prepared from marine algae.
![Research paper thumbnail of Antimycobacterial and antitumor activities of Palladium(II) complexes containing isonicotinamide (isn): X-ray structure of trans-[Pd(N3)2(isn)2]](https://attachments.academia-assets.com/83721726/thumbnails/1.jpg)
](European Journal of Medicinal Chemistry, 2010
Antimicrobial agents and chemotherapy, Aug 15, 2017
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protoz... more Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. Here we report the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N' -dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (IC50 = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (CC50 = 506.0 ± 10.7 μM). Additionally, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, Selective Index = 225), a...
The use of indigenous or remote popular knowledge to identify new drugs against diseases or infec... more The use of indigenous or remote popular knowledge to identify new drugs against diseases or infections is a well-known approach in medicine. The inhabitants of coastal regions are known to prepare algae extracts for the treatment of disorders and ailments such as wounds, fever and stomach aches, as for the prevention of arrhythmia. Recent trends in drug research from natural sources have indicated that marine algae are a promising source of novel biochemically active compounds, especially with antiprotozoal activity. Algae survive in a competitive environment and, therefore, developed defense strategies that have resulted in a significant level of chemical structural diversity in various metabolic pathways. The exploration of these organisms for pharmaceutical and medical purposes has provided important chemical candidates for the discovery of new agents against neglected tropical diseases, stimulating the use of sophisticated physical techniques. This current review describes the main substances biosynthesized by benthic marine algae with activity against Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei; the causative agents of leishmaniasis, Chagas disease and African trypanosomiasis, respectively. Emphasis is given to secondary metabolites and crude extracts prepared from marine algae.
Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms ,... more Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms , or groups of atoms, called ligands. Examples include vitamin B 12 , hemoglobin, chlorophyll, dyes and pigments, as well as catalysts used in organic synthesis. Coordination compounds have received much attention in recent years. This interest was prompted by the discovery that several coordination compounds exhibit activity against bacteria, fungi and cancer. Some coordination compounds are not in clinical use, because of poor water solubility. Because they are unable to cross the lipid membranes of cells, bioavailability and efficacy are low. Some researchers have applied nanotechnology to coordination compounds, hoping to reduce the number of doses required and the severity of side effects, and also to improve biological activity. Nanotechnology can deliver active components in sufficient concentrations throughout treatment, guiding it to the desired location of action; conventional treatments do not meet these requirements. In this study we review some drug delivery systems based on nanotechnology, such as microemulsions (MEs), cyclodextrin (CD), polymeric nanoparticles (PN), solid lipid nanoparticles (SLNs), nanos-tructured lipid carriers (NLCs), magnetic and gold nanoparticles (MNPs / AuNPs) and liquid crystalline systems (LC), and coordination compounds.
The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(d... more The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(dmba)(μ-Cl)] 2 , [Pd(dmba)(NCO)(isn)], [Pd(dmba)(N 3)(isn)] and [Pd(dmba)(μ-NCO)] 2 , (dmba: N,N'-dimethylbenzylamine and isn: isonicotinamide), against the diseases leishmaniasis (Leishmania amazonensis and Leishmania infantum), Chagas disease (Trypanosoma cruzi) and human African trypanosomiasis (Trypanosoma brucei). [Pd(dmba)(μ-NCO)] 2 exhibited good leishmanicidal and trypanocidal activities against L. amazonensis and T. cruzi intracellular amastigote forms, with a 50% inhibitory concentration (IC 50) value of less than 9 μM and selectivity indexes of 14.47 and 28.42, respectively. Stability essays were conducted in phosphate buffer saline (PBS) pH 7.0 and showed that [Pd(dmba)(μ-NCO)] 2 is the most stable molecule. These findings indicate that this compound presented higher selectivity for these parasites than the other tested compounds. The data presented here suggest that this compound should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas disease.
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protoz... more Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N=-dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(-N 3)] 2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC 50 ] 13.2 0.7 M) and decreases the proliferation of intra-cellular amastigotes in in vitro incubated macrophages (IC 50 10.2 2.2 M) without a cytotoxic effect when tested against peritoneal macrophages (50% cy-totoxic concentration 506.0 10.7 M). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC 50 2.3 0.5 M, selective index 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to ampho-tericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore , CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.)
The reactions between [PdCl 2 (tmbiimH 2)]·H 2 O (1) {tmbiimH 2 = 2,2'-bis(4,5-dimethylimidazole)... more The reactions between [PdCl 2 (tmbiimH 2)]·H 2 O (1) {tmbiimH 2 = 2,2'-bis(4,5-dimethylimidazole)} and thiourea (tu), N-methylthiourea (mtu), N-phenylthiourea (ptu), N,N'-dimethylthiourea (dmtu) or N,N'-diphenylthiourea (dptu) in the 1:2 molar ratio resulted in the compounds [PdL 2 (tmbiimH 2)]Cl 2 ·nH 2 O {L = tu (2), mtu (3), ptu (4), dmtu (5) and dptu (6)}, which were characterized by elemental analyses, infrared (IR), and 1 H NMR spectroscopies and conductivity measurements. The IR spectra of 1–6 were consistent with the presence of chelating tmbimH 2 ligand. All compounds and cisplatin were tested in vitro by MTT assay for their cytotoxicity against three murine cancer cell lines: mammary adeno-carcinoma (LM3), lung adenocarcinoma (LP07) and mouse fibroblast (L929) cells. Relating the series of compounds to their biological activities we found compound 6 as the most promising of them.
Química Nova
SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY EVALUATION OF CYCLOPALLADATED COMPOUNDS CONTAI... more SYNTHESIS, CHARACTERIZATION AND CYTOTOXIC ACTIVITY EVALUATION OF CYCLOPALLADATED COMPOUNDS CONTAINING ORTHOMETALLATED BENZALDEHYDEOXIME AND ETHYLENETHIOUREA AS LIGANDS. The halidebridge cleavage reaction of the [Pd(C 2 ,N-bzox)(µ-Cl)] 2 compound (bzox = benzaldehydeoxime) with ethylenethiourea (L) in the 1:2 molar ratio at room temperature yielded the cyclopalladated compound [Pd(C 2 ,N-bzox)(Cl)(L)] (1) whose replacement of the halide group by the addition of suitable salts afforded compounds of general formulae [Pd(C 2 ,N-bzox)(X)(L)] {X = Br-(2), I-(3)}. All compounds were characterized by melting point, elemental analyses, infrared and 1 Hand 13 C{ 1 H}-NMR spectroscopies revealing the complexes formation with the oxime coordinated to Pd(II) as C,N-chelating and the ethylenethiourea as a monodentate ligand via the sulfur atom. The cytotoxicity of cyclopalladated compounds has been evaluated in vitro against murine mammary tumor cell (LM3) showing cytotoxic activity similar to cisplatin.
Revista Brasileira de Farmacognosia, 2014
The use of indigenous or remote popular knowledge to identify new drugs against diseases or infec... more The use of indigenous or remote popular knowledge to identify new drugs against diseases or infections is a well-known approach in medicine. The inhabitants of coastal regions are known to prepare algae extracts for the treatment of disorders and ailments such as wounds, fever and stomach aches, as for the prevention of arrhythmia. Recent trends in drug research from natural sources have indicated that marine algae are a promising source of novel biochemically active compounds, especially with antiprotozoal activity. Algae survive in a competitive environment and, therefore, developed defense strategies that have resulted in a significant level of chemical structural diversity in various metabolic pathways. The exploration of these organisms for pharmaceutical and medical purposes has provided important chemical candidates for the discovery of new agents against neglected tropical diseases, stimulating the use of sophisticated physical techniques. This current review describes the main substances biosynthesized by benthic marine algae with activity against Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei; the causative agents of leishmaniasis, Chagas disease and African trypanosomiasis, respectively. Emphasis is given to secondary metabolites and crude extracts prepared from marine algae.
European Journal of Medicinal Chemistry, 2010
Antimicrobial agents and chemotherapy, Aug 15, 2017
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protoz... more Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. Here we report the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N' -dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (IC50 = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (CC50 = 506.0 ± 10.7 μM). Additionally, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, Selective Index = 225), a...
The use of indigenous or remote popular knowledge to identify new drugs against diseases or infec... more The use of indigenous or remote popular knowledge to identify new drugs against diseases or infections is a well-known approach in medicine. The inhabitants of coastal regions are known to prepare algae extracts for the treatment of disorders and ailments such as wounds, fever and stomach aches, as for the prevention of arrhythmia. Recent trends in drug research from natural sources have indicated that marine algae are a promising source of novel biochemically active compounds, especially with antiprotozoal activity. Algae survive in a competitive environment and, therefore, developed defense strategies that have resulted in a significant level of chemical structural diversity in various metabolic pathways. The exploration of these organisms for pharmaceutical and medical purposes has provided important chemical candidates for the discovery of new agents against neglected tropical diseases, stimulating the use of sophisticated physical techniques. This current review describes the main substances biosynthesized by benthic marine algae with activity against Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei; the causative agents of leishmaniasis, Chagas disease and African trypanosomiasis, respectively. Emphasis is given to secondary metabolites and crude extracts prepared from marine algae.
Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms ,... more Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms , or groups of atoms, called ligands. Examples include vitamin B 12 , hemoglobin, chlorophyll, dyes and pigments, as well as catalysts used in organic synthesis. Coordination compounds have received much attention in recent years. This interest was prompted by the discovery that several coordination compounds exhibit activity against bacteria, fungi and cancer. Some coordination compounds are not in clinical use, because of poor water solubility. Because they are unable to cross the lipid membranes of cells, bioavailability and efficacy are low. Some researchers have applied nanotechnology to coordination compounds, hoping to reduce the number of doses required and the severity of side effects, and also to improve biological activity. Nanotechnology can deliver active components in sufficient concentrations throughout treatment, guiding it to the desired location of action; conventional treatments do not meet these requirements. In this study we review some drug delivery systems based on nanotechnology, such as microemulsions (MEs), cyclodextrin (CD), polymeric nanoparticles (PN), solid lipid nanoparticles (SLNs), nanos-tructured lipid carriers (NLCs), magnetic and gold nanoparticles (MNPs / AuNPs) and liquid crystalline systems (LC), and coordination compounds.
The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(d... more The present study describes the antiprotozoal activities of four cyclopalladated compounds, [Pd(dmba)(μ-Cl)] 2 , [Pd(dmba)(NCO)(isn)], [Pd(dmba)(N 3)(isn)] and [Pd(dmba)(μ-NCO)] 2 , (dmba: N,N'-dimethylbenzylamine and isn: isonicotinamide), against the diseases leishmaniasis (Leishmania amazonensis and Leishmania infantum), Chagas disease (Trypanosoma cruzi) and human African trypanosomiasis (Trypanosoma brucei). [Pd(dmba)(μ-NCO)] 2 exhibited good leishmanicidal and trypanocidal activities against L. amazonensis and T. cruzi intracellular amastigote forms, with a 50% inhibitory concentration (IC 50) value of less than 9 μM and selectivity indexes of 14.47 and 28.42, respectively. Stability essays were conducted in phosphate buffer saline (PBS) pH 7.0 and showed that [Pd(dmba)(μ-NCO)] 2 is the most stable molecule. These findings indicate that this compound presented higher selectivity for these parasites than the other tested compounds. The data presented here suggest that this compound should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas disease.
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protoz... more Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N=-dimethylbenzylamine (Hdmba) against Leishmania amazonensis. The compound [Pd(dmba)(-N 3)] 2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC 50 ] 13.2 0.7 M) and decreases the proliferation of intra-cellular amastigotes in in vitro incubated macrophages (IC 50 10.2 2.2 M) without a cytotoxic effect when tested against peritoneal macrophages (50% cy-totoxic concentration 506.0 10.7 M). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC 50 2.3 0.5 M, selective index 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to ampho-tericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore , CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.)
The reactions between [PdCl 2 (tmbiimH 2)]·H 2 O (1) {tmbiimH 2 = 2,2'-bis(4,5-dimethylimidazole)... more The reactions between [PdCl 2 (tmbiimH 2)]·H 2 O (1) {tmbiimH 2 = 2,2'-bis(4,5-dimethylimidazole)} and thiourea (tu), N-methylthiourea (mtu), N-phenylthiourea (ptu), N,N'-dimethylthiourea (dmtu) or N,N'-diphenylthiourea (dptu) in the 1:2 molar ratio resulted in the compounds [PdL 2 (tmbiimH 2)]Cl 2 ·nH 2 O {L = tu (2), mtu (3), ptu (4), dmtu (5) and dptu (6)}, which were characterized by elemental analyses, infrared (IR), and 1 H NMR spectroscopies and conductivity measurements. The IR spectra of 1–6 were consistent with the presence of chelating tmbimH 2 ligand. All compounds and cisplatin were tested in vitro by MTT assay for their cytotoxicity against three murine cancer cell lines: mammary adeno-carcinoma (LM3), lung adenocarcinoma (LP07) and mouse fibroblast (L929) cells. Relating the series of compounds to their biological activities we found compound 6 as the most promising of them.