Chagas disease (CD) is a parasitic zoonosis endemic in most mainland countries of Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective if received at the early stages of the disease. Only two drugs (benznidazole and nifurtimox) have so far been marketed, and both share various limitations such as variable efficacy, many side effects, and long duration of treatment, thus reducing compliance. The in vitro and in vivo efficacy of poly-aggregated amphotericin B (AmB), encapsulated poly-aggregated AmB in albumin microspheres (AmB-AME), and dimeric AmB-sodium deoxycholate micelles (AmB-NaDC) was evaluated. Dimeric AmB-NaDC exhibited a promising selectivity index (SI = 3164) against amastigotes, which was much higher than those obtained for licensed drugs (benznidazole and nifurtimox). AmB-AME, but not AmB-NaDC, significantly reduced the parasitemia levels (3.6-fold) in comparison to the control group after parenteral administration at day 7 postinfection. However, the oral administration of AmB-NaDC (10-15 mg/kg/day for 10 days) resulted in a 75% reduction of parasitemia levels and prolonged the survival rate in 100% of the tested animals. Thus, the results presented here illustrate for the first time the oral efficacy of AmB in the treatment of trypanosomiasis. AmB-NaDC is an easily scalable, affordable formulation prepared from GRAS excipients, enabling treatment access worldwide, and therefore it can be regarded as a promising therapy for trypanosomiasis.
The aim of this study was to evaluate the chemical profile and antioxidant, antimicrobial and antiparasitic activities of the hydroalcoholic extract of the leaves of Ziziphus joazeiro Mart. (HELZJ). The antioxidant DPPH and FRAP assays and chemical profile were determined by colorimetric methods and HPLC/DAD. The antiparasitic, antibiotic and antibiotic-modifying activity were evaluated by microdilution assays. The HPLC-DAD assay showed the presence of mostly tannins and flavonoids, such as caffeic acid and quercetin. The levels of polyphenols and flavonoids were 183.136 mg/g extract and 7.37 mg/g extract, respectively. DPPH and FRAP showed low antioxidant activity for the extract. The antibacterial and antifungal activities were not of clinical relevance, showing MIC>1024 μg/mL. However, synergism was observed between HELZJ and the antibiotics amikacin and gentamicin, which resulted in decreased bacterial drug resistance. EHFZJ showed low toxicity in fibroblasts in vitro, while antiparasitic results against Trypnosoma cruzi, Leishmania braziliensis and Leishmania infantum were not clinically relevant. Thus, our results indicate that Z. joazeiro Mart. (HELZJ) could be a source of plant-derived natural products that could lead to the development of promising new antibiotic compounds for infectious diseases.
We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.
A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM–25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity.
Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.