Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives

Freitas, Rosana Helena C. N.; Barbosa, Juliana M. C.; Bernardino, Patrícia; Sueth-Santiago, Vitor; Wardell, Solange M. S. V.; Wardell, Jámes L.; Decotè-Ricardo, Débora; Melo, Tatiana G.; Silva, Edson F. da; Salomão, Kelly; Fraga, Carlos A.M.

doi:10.1016/j.biopha.2020.110162

Cited by 11 publications

(7 citation statements)

References 44 publications

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“…In addition, supernatants were collected, and released parasites were counted daily in a Neubauer chamber. The result was expressed by the infection index (II), which corresponds to the multiplication of the percentage of infection by the number of parasites/infected cells ( Freitas et al., 2020 ). The IC 50 values were calculated for the different days of treatment, corresponding to the concentration that led to 50% inhibition of this parameter (IC 50 II).…”

Section: Methodsmentioning

confidence: 99%

Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells

Barbosa

Pedra-Rezende

Pereira

et al. 2022

Front. Cell. Infect. Microbiol.

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Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz) and nifurtimox (Nif), both presenting relevant limitations. Different approaches have been employed to establish more effective and safer schemes to treat T. cruzi infection, mostly based on drug repurposing and combination therapies. Amiodarone (AMD), an antiarrhythmic medicament of choice for patients with the chronic cardiac form of CD, is also recognized as a trypanocidal agent. Therefore, our aim is to investigate the combined treatment Bz + AMD on trypomastigote viability, control of T. cruzi intracellular form proliferation, and recovery of the infection-induced cytoskeleton alterations in cardiac cells. The combination of Bz + AMD did not improve the direct trypanocidal effect of AMD on the infective blood trypomastigote and replicative intracellular forms of the parasite. Otherwise, the treatment of T. cruzi-infected cardiac cells with Bz plus AMD attenuated the infection-triggered cytoskeleton damage of host cells and the cytotoxic effects of AMD. Thus, the combined treatment Bz + AMD may favor parasite control and hamper tissue damage.

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Section: Methodsmentioning

confidence: 99%

Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells

Barbosa

Pedra-Rezende

Pereira

et al. 2022

Front. Cell. Infect. Microbiol.

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“…All experiments dealing with animals were performed in accordance with Brazilian Law 11.794/2008 and regulations of the National Council of Animal Experimentation Control under license L038/2018 from the Ethics Committee for Animal Use of the Oswaldo Cruz Institute (CEUA/IOC). Male mice between 3-4 weeks were housed at a maximum of 5 individuals per cage, kept in a specific-pathogen-free (SPF) room at 20 to 22˚C under a 12/12 h light/dark cycle at 50 to 60% humidity and provided sterilized water and chow ad libitum [39]. The animals will be euthanized to obtain the parasites on the eighth day after infection to carry out the experiments.…”

Section: Biological Activitymentioning

confidence: 99%

“…The cultures were fixed and stained with Diff-Quick (Laborclin) and examined by light microscopy to determine the percent infected cells and infection index (II), which corresponds to the number of parasites/100 cells [43]. The results are also expressed using the IC 50 /24 h, which corresponds to the concentration that produces a 50% decrease in the II [39].…”

Section: In Vitro Activity Of β-Lap:cd and β-Lap Against The Y Strainmentioning

confidence: 99%

“…The samples were dehydrated in an ascending acetone series and embedded in Polybed 812 resin. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a JEOL JEM1011 transmission electron microscope (Tokyo, Japan) (Technological Platform of Electronic Microscopy at the Institute of Oswaldo Cruz) [39].…”

Section: Transmission Electron Microscopy Analysismentioning

confidence: 99%

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Characterization and trypanocidal activity of a β-lapachone-containing drug carrier

et al. 2021

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The treatment of Chagas disease (CD), a neglected parasitic condition caused by Trypanosoma cruzi, is still based on only two drugs, nifurtimox (Nif) and benznidazole (Bz), both of which have limited efficacy in the late chronic phase and induce severe side effects. This scenario justifies the continuous search for alternative drugs, and in this context, the natural naphthoquinone β-lapachone (β-Lap) and its derivatives have demonstrated important trypanocidal activities. Unfortunately, the decrease in trypanocidal activity in the blood, high toxicity to mammalian cells and low water solubility of β-Lap limit its systemic administration and, consequently, clinical applications. For this reason, carriers as drug delivery systems can strategically maximize the therapeutic effects of this drug, overcoming the above mentioned restrictions. Accordingly, the aim of this study is to investigate the in vitro anti-T. cruzi effects of β-Lap encapsulated in2-hydroxypropyl-β-cyclodextrin (2HP-β-CD) and its potential toxicity to mammalian cells.

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“…Also, the sulfur atom in this heterocycle imparts improved liposolubility. More specifically, 2-amino-1,3,4thiadiazole series (Jain et al, 2013;Martins et al, 2016;Vandresen et al, 2017;Serban, 2019;Freitas et al, 2020) and their thiosemicarbazone analogue (De Melos et al, 2015;Batista et al, 2019) have been studied for potential antileishmanial and trypanocidal activity ( Figures 1C-E). Comparing the results reported for compounds IV and V, the 2-amino-1,3,4-thiadiazole derivatives were less active than the thiosemicarbazone derivatives ( Figures 1C, D).…”

Section: Introductionmentioning

confidence: 99%

Antiparasitic Behavior of Trifluoromethylated Pyrazole 2-Amino-1,3,4-thiadiazole Hybrids and Their Analogues: Synthesis and Structure-Activity Relationship

et al. 2020

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A series of trifluoromethylated pyrazole thiosemicarbazone, trifluromethylated pyrazole isothiosemicarbazone, and trifluoromethylated pyrazole 2-amino-1,3,4-thiadiazole hybrids were synthesized and evaluated in vitro against the promastigote form of Leishmania amazonensis and the epimastigote form of Trypanosoma cruzi, the pathogens causing the neglected tropical diseases leishmaniasis and Chagas disease, respectively. The results show the potential of these compounds regarding their antiparasitic properties. Studies on the structure-activity relationship demonstrated that compounds containing a bulky group at the para position of the phenyl ring attached to the 5-position of the pyrazole core had better antiparasitic effects. Among the substituents attached at the 3-position of the pyrazole ring, the insertion of the 2-amino-1,3,4thiadiazole nucleus led to the most potent compounds compared to the thiosemicarbazone derivative.

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Synthesis and trypanocidal activity of novel pyridinyl-1,3,4-thiadiazole derivatives

Cited by 11 publications

References 44 publications

Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells

Benznidazole and amiodarone combined treatment attenuates cytoskeletal damage in Trypanosoma cruzi-infected cardiac cells

Characterization and trypanocidal activity of a β-lapachone-containing drug carrier

Antiparasitic Behavior of Trifluoromethylated Pyrazole 2-Amino-1,3,4-thiadiazole Hybrids and Their Analogues: Synthesis and Structure-Activity Relationship

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