Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells

Faria, Robson Xavier; Gonzaga, Daniel T. G.; Pacheco, Paulo; Souza, André Luis Almeida; Ferreira, Vı́tor F.; Silva, Fernando de Carvalho da

doi:10.1007/s10863-018-9746-z

Cited by 9 publications

(4 citation statements)

References 51 publications

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“…In our experimental conditions the compounds 52 , 53 and 54 weren’t able to be solubilized. This information can be important for future studies [ 30 , 31 , 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

et al. 2020

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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 cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (9, 13, 19, 22, 24, 29), showed no toxicity at the tested concentrations.

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“…In our experimental conditions the compounds 52 , 53 and 54 weren’t able to be solubilized. This information can be important for future studies [ 30 , 31 , 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

et al. 2020

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“…DHE is used to capture the cellular ROS and form fluorescent product. Briefly, H9C2 cells were cultured at 6well plates to complete confluence; the cells were then stained with 1 mM DHE for 30 min [15]. The morphometric record of stained cells was done on a Leica confocal microscope equipped with a digital camera.…”

Section: Reactive Oxygen Species (Ros) Assaymentioning

confidence: 99%

DPP-4 inhibitor anagliptin protects against hypoxia-induced cytotoxicity in cardiac H9C2 cells

Wang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…The role of the triazole group against T. cruzi is not so clear, since just four out of seven compounds present this substituent. However, triazole-based drugs have also been described as possessing high in vitro activity against T. cruzi [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi

et al. 2021

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Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.

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Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells

Cited by 9 publications

References 51 publications

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

DPP-4 inhibitor anagliptin protects against hypoxia-induced cytotoxicity in cardiac H9C2 cells

Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi

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