Pharmacological Approaches to Antitrypanosomal Chemotherapy

Croft, Simon L.

doi:10.1590/s0074-02761999000200017

Cited by 46 publications

(29 citation statements)

References 41 publications

(38 reference statements)

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“…All the complexes presented ligands 7HtpO: 4,7 dihydro-7-oxo- [1,2,4] [4, H]leucine (specific activity 35-70 Ci/mmol), obtained from the Radiochemical Center (UK). The number of parasites in all cases was 7 !…”

Section: Newly Synthesized Compounds Assayedmentioning

confidence: 99%

“…Both pathologies are considered a health problem in America and Africa, respectively [1]. Currently, strategies to control American trypanosomiasis (or Chagas disease) and African sleeping sickness include the development of new drugs, as the existing ones present variable effectiveness, and the kinetoplastids have developed resistance against them [2].…”

Section: Introductionmentioning

confidence: 99%

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Activities of Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against Trypanosoma cruzi and T. brucei brucei

et al. 2004

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We studied the biological activity of three newly synthesized metal complexes of triazole-pyrimidine derivatives that were previously observed to inhibit in vitro growth of epimastigotes of Trypanosoma cruzi and procyclic forms of Trypanosoma bruceibrucei. We analyzed the possible inhibitory effect of these compounds on the synthesis of DNA, RNA and protein, ultrastructure and excretion of metabolites by these parasites. RNA synthesis was inhibited by all three complexes assayed. These complexes also led to anomalies of the main organelles (e.g. nucleus, kinetoplast and mitochondria). In addition, these complexes may be capable of altering the excretion of metabolites by the parasites.

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Section: Newly Synthesized Compounds Assayedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activities of Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against Trypanosoma cruzi and T. brucei brucei

et al. 2004

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“…Both drugs have serious side effects, including vomiting, peripheral polyneuropathy, and allergic dermopathy (De Castro 1993;Rassi and Luquetti 1992;Croft et al 1997), probably as a consequence of oxidative or reductive damage in the host tissues (Urbina and Docampo 2003). Some new drugs already in test for treating this parasitic infection may have a promising future (Stoppani 1999;Croft 1999), but the lack of selective cytotoxicity against T. cruzi makes the search for new products a priority in the medical field (Sepúlveda-Boza and Cassels 1996).…”

Section: Introductionmentioning

confidence: 99%

Effect of oregano (Origanum vulgare L.) and thyme (Thymus vulgaris L.) essential oils on Trypanosoma cruzi (Protozoa: Kinetoplastida) growth and ultrastructure

et al. 2006

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In the present work, we have investigated the effect of essential oils obtained from Origanum vulgare L. (oregano) and Thymus vulgaris L. (thyme) on growth and ultrastructure of diverse evolutive forms of Trypanosoma cruzi. Culture epimastigotes and bloodstream trypomastigotes were incubated for 24 h with different concentrations of oregano or thyme essential oils and with thymol (the main constituent of thyme), and the inhibitory concentration (IC)(50) was determined by cell counting. Crude extract of oregano essential oil inhibited epimastigote growth (IC(50)/24 h = 175 microg/ml) and also induced trypomastigote lysis (IC(50)/24 h = 115 microg/ml). Thyme essential oil presented IC(50)/24 h values of 77 microg/ml for epimastigotes and 38 mug/ml for trypomastigotes, while treatment with thymol resulted in an IC(50)/24 h of 62 microg/ml for epimastigotes and 53 microg/ml for trypomastigotes. Scanning electron microscopy of treated cells showed few morphological alterations at the plasma membrane. Observation by transmission electron microscopy showed cytoplasmic swelling with occasional morphological alterations in plasma and flagellar membrane. Our data indicate that oregano and thyme essential oils are effective against T. cruzi, with higher activity of thyme, and that thymol may be the main component responsible for the trypanocidal activity.

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“…Treatment for stage 1, when the parasites are limited to the hemolymphatic system, is administration of pentamidine (T. b. gambiense) or suramin (T. b. rhodesiense). In stage 2, or central nervous system (CNS) disease, either melarsoprol (T. b. gambiense and T. b. rhodesiense) or eflornithine (T. b. gambiense) is used (14). Melarsoprol kills 5 to 10% of patients (32), and treatment failures of up to 25% have been reported (12,13).…”

mentioning

confidence: 99%

Discovery of Novel Orally Bioavailable Oxaborole 6-Carboxamides That Demonstrate Cure in a Murine Model of Late-Stage Central Nervous System African Trypanosomiasis

Nare

Wring

Bacchi

et al. 2010

Antimicrob Agents Chemother

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(32), and treatment failures of up to 25% have been reported (12, 13). Difluoromethylornithine (DFMO) (Ornidyl) requires a 2-week therapy regimen which is difficult to administer in rural clinics (34). A new combination therapy with DFMO and oral nifurtimox (NECT) reduces the dose time to 1 week but still requires intravenous (i.v.) dosing (35).Antigenic variation is frequent, rendering prospects for vaccine development impracticable (22,27). What is urgently needed is a safe, orally (p.o.) administered drug, effective against both stages 1 and 2 of HAT, which then eliminates the need for staging and raises the potential for the eradication of sleeping sickness. Toward this aspiration, we have identified a class of boron-containing compounds, oxaborole carboxamides, as novel leads that show potent and selective trypanocidal activity in vitro. Two examples chosen from this lead series are AN3520 and SCYX-6759. These compounds exhibit rapid,

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Pharmacological Approaches to Antitrypanosomal Chemotherapy

Cited by 46 publications

References 41 publications

Activities of Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against <i>Trypanosoma cruzi</i> and <i>T. brucei brucei</i>

Activities of Pt(II) and Ru(III) Triazole-Pyrimidine Complexes against <i>Trypanosoma cruzi</i> and <i>T. brucei brucei</i>

Effect of oregano (Origanum vulgare L.) and thyme (Thymus vulgaris L.) essential oils on Trypanosoma cruzi (Protozoa: Kinetoplastida) growth and ultrastructure

Discovery of Novel Orally Bioavailable Oxaborole 6-Carboxamides That Demonstrate Cure in a Murine Model of Late-Stage Central Nervous System African Trypanosomiasis

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