In vitro evaluation of antitrypanosomal activity and molecular docking of benzoylthioureas

Pereira, Patrícia Morais Lopes; Camargo, Priscila Goes; Fernandes, Bruna Terci; Flores-Junior, Luiz A.P.; Dias, Luiza R.S.; Lima, Camilo Henrique da Silva; Pinge‐Filho, Phileno; Lioni, Lucy Megumi Yamauchi; Yamada‐Ogatta, Sueli Fumie; Bispo, Marcelle de Lima Ferreira; Macedo, Fernando

doi:10.1016/j.parint.2020.102225

Cited by 10 publications

(11 citation statements)

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“…Tests containing only the medium or medium plus 1% DMSO were used as an untreated control in all assays. The BTU concentrations causing 50% (IC 50 : BTU-1 = 26.4; BTU-2 = 13.4; and BTU-3 = 61.1 µM) and 90% (IC 90 : BTU-1 = 81.65; BTU-2 = 48.37; and BTU-3 = 264.9 µM) growth inhibition after 72 h were previously determined [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

“…Epimastigotes were inoculated into a 24-well plate containing LIT+FBS, along with BTU-1 (26.4 µM), BTU-2 (13.4 µM) or BTU-3 (61.1 µM), which correspond to the IC 50 values after 72 h (IC 50/72 h ) of incubation, determined previously [ 23 ]. Cell growth was estimated by direct counting using a hemocytometer (Improved Double Neubauer) every 24 h, up to a period of 96 h. Wells containing growth medium alone or growth medium plus 1% DMSO served as controls.…”

Section: Methodsmentioning

confidence: 99%

“…Thiourea derivatives have shown promising pharmaceutical potential due to their diverse pharmacological activities, including antitumoral [ 11 ], antioxidant [ 12 ], antidiabetic [ 13 ], and antimicrobial [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ] properties. Notably, the thiourea moiety has been identified in several compounds with potential for the development of new therapeutic compounds to treat diseases caused by trypanosomatid species [ 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…In a previous study, we assessed the antiprotozoal activity of sixteen benzoylthiourea derivatives against T. cruzi Y strain [ 23 ]. Among them, N -(cyclohexylcarbamothioyl) benzamide ( BTU-1 ), N -( tert -butylcarbamothioyl) benzamide ( BTU-2 ), and 4-bromo- N -(3-nitrophenyl) carbamothioyl benzamide ( BTU-3 ) exhibited selective antiprotozoal activity against T. cruzi , inhibiting the proliferation of epimastigotes and amastigotes, as well as the viability of trypomastigotes, in non-toxic concentrations to mammalian cells [ 23 ]. In this study, we further investigated the antiprotozoal activity of BTU-1 , BTU-2 , and BTU-3 against T. cruzi Y strain and suggested a potential mechanism of action involved in parasite death.…”

Section: Introductionmentioning

confidence: 99%

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Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action

et al. 2023

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For decades, only two nitroheterocyclic drugs have been used as therapeutic agents for Chagas disease. However, these drugs present limited effectiveness during the chronic phase, possess unfavorable pharmacokinetic properties, and induce severe adverse effects, resulting in low treatment adherence. A previous study reported that N-(cyclohexylcarbamothioyl) benzamide (BTU-1), N-(tert-butylcarbamothioyl) benzamide (BTU-2), and (4-bromo-N-(3-nitrophenyl) carbamothioyl benzamide (BTU-3) present selective antiprotozoal activity against all developmental forms of Trypanosoma cruzi Y strain. In this study, we investigated the mechanism of action of these compounds through microscopy and biochemical analyses. Transmission electron microscopy analysis showed nuclear disorganization, changes in the plasma membrane with the appearance of blebs and extracellular arrangements, intense vacuolization, mitochondrial swelling, and formation of myelin-like structures. Biochemical results showed changes in the mitochondrial membrane potential, reactive oxygen species content, lipid peroxidation, and plasma membrane fluidity. In addition, the formation of autophagic vacuoles was observed. These findings indicate that BTU-1, BTU-2, and BTU-3 induced profound morphological, ultrastructural, and biochemical alterations in epimastigote forms, triggering an autophagic-dependent cell death pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action

et al. 2023

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“…Thiourea is a class of organic compounds containing the > NC = SN < moiety that allows many chemical modifications and bonding possibilities due to the presence of nitrogen and sulfur atoms ( Zahra et al, 2022 ). Several biological activities have been attributed to thiourea derivatives, including antibacterial, antifungal, antitrypanosomal, antidiabetic, antitumor, and urease inhibitor ( Rego et al, 2018 ; Brito et al, 2020 ; Khidre and Radini, 2021 ; Pereira et al, 2021 ; Biasi-Garbin et al, 2022 ; Zahra et al, 2022 ) among others. Thiourea derivatives are thermally stable and can be produced with good efficiency from available starting compounds by simple and low-cost reactions ( Shakeel, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Synergistic antifungal interaction of N-(butylcarbamothioyl) benzamide and amphotericin B against Cryptococcus neoformans

Andriani

Spoladori²,

Fábris³

et al. 2023

Front. Microbiol.

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IntroductionCryptococcus neoformans is one of the leading causes of invasive fungal infections worldwide. Cryptococcal meningoencephalitis is the main challenge of antifungal therapy due to high morbidity and mortality rates, especially in low- and middle-income countries. This can be partly attributed to the lack of specific diagnosis difficulty accessing treatment, antifungal resistance and antifungal toxicity.MethodsIn the present study, the effect of the synthetic thiourea derivative N-(butylcarbamothioyl) benzamide (BTU-01), alone and combined with amphotericin B (AmB), was evaluated in planktonic and sessile (biofilm) cells of C. neoformans.ResultsBTU-01 alone exhibited a fungistatic activity with minimal inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL for planktonic cells; and sessile MICs ranging from 125.0 to 1000.0 μg/mL. BTU-01 caused a concentration-dependent inhibitory activity on cryptococcal urease and did not interfere with plasma membrane fluidity. Molecular docking was performed on Canavalia ensiformis urease, and BTU-01 showed relevant interactions with the enzyme. The combination of BTU-01 and AmB exhibited synergistic fungicidal activity against planktonic and sessile cells of C. neoformans. Microscopic analysis of C. neoformans treated with BTU-01, alone or combined with AmB, revealed a reduction in cell and capsule sizes, changes in the morphology of planktonic cells; a significant decrease in the number of cells within the biofilm; and absence of exopolymeric matrix surrounding the sessile cells. Neither hemolytic activity nor cytotoxicity to mammalian cells was detected for BTU-01, alone or combined with AmB, at concentrations that exhibited antifungal activity. BTU-01 also displayed drug-likeness properties.ConclusionThese results indicate the potential of BTU-01, for the development of new strategies for controlling C. neoformans infections.

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Examination of multiple Trypanosoma cruzi targets in a new drug discovery approach for Chagas disease

Beltran-Hortelano

Alcolea

Font

et al. 2022

Bioorganic & Medicinal Chemistry

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In vitro evaluation of antitrypanosomal activity and molecular docking of benzoylthioureas

Cited by 10 publications

References 44 publications

Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action

Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action

Synergistic antifungal interaction of N-(butylcarbamothioyl) benzamide and amphotericin B against Cryptococcus neoformans

Examination of multiple Trypanosoma cruzi targets in a new drug discovery approach for Chagas disease

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