Leishmanicidal Activities of Novel Synthetic Furoxan and Benzofuroxan Derivatives

Dutra, Luiz Antônio; Almeida, Letícia de; Passalacqua, Thaís Gaban; Reis, Juliana Santana; Torres, Fábio Aurélio Esteves; Martínez, Isabel; Peccinini, Rosângela Gonçalves; Chin, Chung Man; Chegaev, Konstantin; Guglielmo, Stefano; Fruttero, Roberta; Graminha, Márcia Aparecida Silva; Santos, Jean Leandro dos

doi:10.1128/aac.00052-14

Cited by 49 publications

(60 citation statements)

References 59 publications

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“…The cyclopalladated complexes were tested against L. amazonensis, L. infantum (promastigote and amastigote), T. cruzi (epimastigote and amastigote) and T. brucei (procyclic forms) using the MTT colorimetric assay [44][45][46] and an in vitro intracellular amastigote assay 43,49,50 to evaluate the antiprotozoal activity. Amphotericin B and pentamidine were included in the assays as positive controls for Leishmania species, benznidazole for T. cruzi and pentamidine for T. brucei.…”

Section: Resultsmentioning

confidence: 99%

“…43 Adult male Swiss albino mice (20 to 35 g) were used in the experiments. They were housed in single-sex cages under a 12 h light/12 h dark cycle in a controlled-temperature room (22 ± 2 °C).…”

Section: Cytotoxicity Using Murine Macrophagesmentioning

confidence: 99%

“…43 Murine peritoneal macrophages were plated at 3 × 10 5 cells per well on coverslips (13 mm diameter) previously arranged in a 24 well plate in RPMI 1640 medium 44 supplemented with 10% inactivated FBS and allowed to adhere for 4 h at 37 ± 2 °C in 5% CO 2 . Adherent macrophages were infected with Leishmania promastigotes in the stationary growth phase or T. cruzi trypomastigote using a ratio of 5/10:1 parasites per cell (L. amazonensis or L. infantum/T.…”

Section: Leishmanicidal and Trypanocidal Activities Against Intracellmentioning

confidence: 99%

“…The compounds were tested in different concentrations and incubated at 28 ± 2 °C for 72 h for L. amazonensis, L. infantum and T. cruzi and 24 h for T. brucei. 23,43 The assays were carried out in triplicates. Absorbance was read in a 96-well plate reader (Robonik) at 490 nm for Leishmania species and 595 nm for T. cruzi and T. brucei.…”

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Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Velásquez¹,

Souza²,

Passalacqua³

et al. 2015

Journal of the Brazilian Chemical Society

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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. 7 Pentavalent antimonial drugs are the most frequently prescribed treatments for leishmaniasis. 8 The main adverse effects that occur in systemic administration of these antimonials are arthralgias, myalgias, anorexia, and nausea, and other serious side effects include pancreatitis, liver-enzyme abnormalities, cardiac malfunctions and severe renal toxic effects. Other drugs, such as amphotericin B, pentamidine and miltefosine, are second choice drugs but they also produce side effects that can endanger the patient's life. KeywordsTrypanosoma cruzi is the causative agent of Chagas disease, which is present mainly in Latin America but also in North America. [10][11][12] Nifurtimox and benznidazole are the only drugs available to treat patients in the acute phase of the disease.13,14 However, these drugs are not Velásquez et al. 1033 Vol. 27, No. 6, 2016 effective against the chronic phase of the disease, and they present multiple side effects, from dermatitis to bone marrow depression. 15 HAT is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. 16Treatment of the hemolymphatic stage of HAT relies on suramin and pentamidine. In the meningoencephalitis stage, melarsoprol, a highly toxic arsenic-based drug that is effective against both T. b. gambiense and T. b. rhodesiense is used. Eflornithine is useful only against T. b. gambiense. An eflornithine/nifurtimox combined therapy has been used, but this also causes several side effects.17 In summary, the conventional drugs that have been employed to treat these diseases are antiquated, have high toxicity and are ineffective due to drug resistance. Therefore, is critical to develop new drugs for the treatment of these trypanosomiases.The use of transition metal-based drugs is increasing significantly in the therapy of cancer and tropical diseases; in fact, many organometallic compounds have been designed to specifically bind to a well-d...

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Section: Resultsmentioning

confidence: 99%

Section: Cytotoxicity Using Murine Macrophagesmentioning

confidence: 99%

Section: Leishmanicidal and Trypanocidal Activities Against Intracellmentioning

confidence: 99%

mentioning

confidence: 99%

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Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Velásquez¹,

Souza²,

Passalacqua³

et al. 2015

Journal of the Brazilian Chemical Society

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“…The compounds 1, 2a, 2b, 5, 6, 10 and 13 were synthesized according to a previously described methodology [4][5][6][7][8][9]. of aminoguanidine hydrochloride (45mg; 0,4mmol) and 3mL of ethanol was stirred at room temperature for 2 to 3h and monitored by TLC (100% ethyl acetate).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, biological evaluation and bioavailability prediction of novel furoxan derivatives as leishmanicidal compounds

Pavan

Almeida

Passalacqua

et al. 2017

Proceedings of the 21st International Electronic Conference on Synthetic Organic Chemistry

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Four novel furoxan derivatives were synthesized, characterized and evaluated for in vitro activity against promastigote form of Leishmania amazonensis and Leishmania infantum, and amastigote form of L. infantum. Compound 7 presented low cytotoxicity, being 30 times less toxic than pentamidine. All compounds were more active against L. infantum than L. amazonensis promastigote form, with IC50 reaching values around 8 µM.Regarding amastigote form of L. infantum, the compounds (3b and 7) have exhibited IC50 values around 60 µM. The in silico prediction of ADME properties has shown that all compounds demonstrated drugability according to 'Lipinski rules' and presented intestinal absorption ranging from 67 to 70%. In conclusion, the compounds presented here have demonstrated to be interesting prototypes against the visceral form of leishmaniasis.

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Annotation of GC‐MS Data of Antimicrobial Constituents in the Antarctic Seaweed Phaeurus antarcticus by Molecular Networking

dos Santos,

Sousa Teixeira,

da Costa Clementino

et al. 2023

Chemistry & Biodiversity

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Phaeurus antarcticus is a member of the Desmarestiaceae family endemic to the Antarctic Peninsula. Reports addressing its chemical composition and biological activities are scarce. Herein, bioactive non‐polar compounds of P. antarcticus against pathogenic bacteria, Leishmania amazonensis and Neospora caninum parasites were targeted through GC‐MS Molecular Networking and multivariate analysis (OPLS‐DA). The effects on horseradish peroxidase (HRP) were also evaluated. P. antarcticus exhibited selective bacteriostatic and bactericidal activities against Staphylococcus aureus with MIC and MBC values from 6.25 – 100 µg.mL‐1. Fractions HX‐FC and HX‐FD were the most active against L. amazonensis with EC50 ranging from 18.5 – 62.3 µg.mL‐1. Additionally, fractions HX‐FC and HX‐FD showed potent inhibition of N. caninum at EC50 values of 2.8 and 6.3 µg.mL‐1, respectively. All fractions inhibited HRP activity, indicating possible interactions with Heme proteins. It was possible to annotate compounds from tree mains clusters, containing terpenoids, steroids, fatty acids, and alcohols by correlating the spectral data of the GC‐MS analysis with Molecular Networking and the OPLS‐DA results.

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Leishmanicidal Activities of Novel Synthetic Furoxan and Benzofuroxan Derivatives

Cited by 49 publications

References 59 publications

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Antiprotozoal Activity of the Cyclopalladated Complexes AgainstLeishmania amazonensisandTrypanosoma cruzi

Synthesis, biological evaluation and bioavailability prediction of novel furoxan derivatives as leishmanicidal compounds

Annotation of GC‐MS Data of Antimicrobial Constituents in the Antarctic Seaweed Phaeurus antarcticus by Molecular Networking

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