Pyrazol(in)e Derivatives of Curcumin Analogs As a New Class of Anti-
            <i>Trypanosoma Cruzi</i>
            Agents

Matiadis, Dimitris; Saporiti, Tatiana; Aguilera, Elena; Robert, Xavier; Guillon, Christophe; Cabrera, Nallely; Pérez‐Montfort, Ruy; Sagnou, Marina; Álvarez, Guzmán

doi:10.4155/fmc-2020-0349

Cited by 5 publications

(5 citation statements)

References 45 publications

(45 reference statements)

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“…Matiadis et al (2021) synthesized fifteen new pyrazol(in)e derivatives of CUR and two of them, the 4a ( 8 ), ( E )-7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2 H -indazole, and 4e ( 9 ), ( E )-7-(4-fluorobenzylidene)-3-(4-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2 H -indazole, showed 16-fold (for 4a) and 6-fold (for 4e) higher potencies against Tc TIM ( T. cruzi triosephosphate isomerase) and epimastigotes of T. cruzi . in comparison to their curcuminoid precursors [ 117 ] ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Imperador¹,

Scarim

Bosquesi

et al. 2022

Pharmaceuticals

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Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage—characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease’s progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease’s severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.

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Section: Discussionmentioning

confidence: 99%

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Imperador¹,

Scarim

Bosquesi

et al. 2022

Pharmaceuticals

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“…Curcumin and curcumin derivatives have so far been extensively studied for therapeutic purposes, especially in parasitic infections ( Din et al, 2016 ). A successful development of a new class of curcumin has been reported against Trypanosoma cruzi ( Matiadis et al, 2021 ). In Plasmodium infection, several strategies have been developed to increase the effectiveness of curcumin for example nanotized curcumin ( Ghosh et al, 2014 ), curcumin containing liposomes ( Martí Coma-Cros et al, 2018 ), among others.…”

Section: Discussionmentioning

confidence: 99%

Curcumin effect on Acanthamoeba triangularis encystation under nutrient starvation

Boonhok

Sangkanu

Phumjan

et al. 2022

PeerJ

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Background Curcumin is an active compound derived from turmeric, Curcuma longa, and is known for its benefits to human health. The amoebicidal activity of curcumin against Acanthamoeba triangularis was recently discovered. However, a physiological change of intracellular pathways related to A. triangularis encystation mechanism, including autophagy in the surviving amoeba after curcumin treatment, has never been reported. This study aims to investigate the effect of curcumin on the survival of A. triangularis under nutrient starvation and nutrient-rich condition, as well as to evaluate the A. triangularis encystation and a physiological change of Acanthamoeba autophagy at the mRNA level. Methods In this study, A. triangularis amoebas were treated with a sublethal dose of curcumin under nutrient starvation and nutrient-rich condition and the surviving amoebas was investigated. Cysts formation and vacuolization were examined by microscopy and transcriptional expression of autophagy-related genes and other encystation-related genes were evaluated by real-time PCR. Results A. triangularis cysts were formed under nutrient starvation. However, in the presence of the autophagy inhibitor, 3-methyladenine (3-MA), the percentage of cysts was significantly reduced. Interestingly, in the presence of curcumin, most of the parasites remained in the trophozoite stage in both the starvation and nutrient-rich condition. In vacuolization analysis, the percentage of amoebas with enlarged vacuole was increased upon starvation. However, the percentage was significantly declined in the presence of curcumin and 3-MA. Molecular analysis of A. triangularis autophagy-related (ATG) genes showed that the mRNA expression of the ATG genes, ATG3, ATG8b, ATG12, ATG16, under the starvation with curcumin was at a basal level along the treatment. The results were similar to those of the curcumin-treated amoebas under a nutrient-rich condition, except AcATG16 which increased later. On the other hand, mRNA expression of encystation-related genes, cellulose synthase and serine proteinase, remained unchanged during the first 18 h, but significantly increased at 24 h post treatment. Conclusion Curcumin inhibits cyst formation in surviving trophozoites, which may result from its effect on mRNA expression of key Acanthamoeba ATG-related genes. However, further investigation into the mechanism of curcumin in A. triangularis trophozoites arrest and its association with autophagy or other encystation-related pathways is needed to support the future use of curcumin.

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“…The predictions were performed as described before [ 42 ] with the open-access SwissADME software ( http://www.swissadme.ch , accessed on 25 February 2020), a tool that allows the prediction of different pharmacokinetic parameters such as water solubility, lipophilicity, gastrointestinal absorption, bioavailability, etc. (see supporting information).…”

Section: Methodsmentioning

confidence: 99%

“…The predictions were performed as described before [42] with the open-access SwissADME software (http:// www. swiss adme.…”

Section: Calculation Of the Pharmacokinetic Parameters [40 41]mentioning

confidence: 99%

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo

Álvarez

Pul

Robert

et al. 2022

BMC Pharmacol Toxicol

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The capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro. Representatives of the most promising families of compounds were then tested for their ability to inhibit HIV-1 replication in cellulo. From these molecules, a hit compound from the benzimidazole family with high metabolic stability and low toxicity, 2-(4-N,N-dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole (696), appeared to block HIV-1 replication with an IC50 of 3 µM. Quantitative PCR experiments demonstrated that 696 does not block HIV-1 infection before the end of reverse transcription, and molecular docking confirmed that 696 is likely to bind at the interface between two monomers of CA and interfere with capsid oligomerization. Altogether, 696 represents a promising lead molecule for the development of a new series of HIV-1 inhibitors.

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Pyrazol(in)e Derivatives of Curcumin Analogs As a New Class of Anti- Trypanosoma Cruzi Agents

Cited by 5 publications

References 45 publications

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Curcumin effect on Acanthamoeba triangularis encystation under nutrient starvation

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo

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