Current trends in the pharmacological management of Chagas disease

International Journal for Parasitology Drugs and Drug Resistance, Journal Year: 2019, Volume and Issue: 12, P. 7 - 17

Published: Dec. 10, 2019

Chagas disease (CD) is a tropical neglected illness, affecting mainly populations of low socioeconomic status in Latin America. An estimated 6 to 8 million people worldwide are infected with Trypanosoma cruzi, the etiological agent CD. Despite being one main global health problems, this continues without effective treatment during chronic phase infection. The limitation therapeutic strategies has been biggest challenges on fight against Nifurtimox and benznidazole, developed 1970s, still only commercial options established efficacy However, these drugs have proven early infection benefits questionable. Consequently, there growing need for new pharmacological alternatives, either by optimization existing or formulation compounds. In present study, literature review currently adopted therapy, its concomitant combination other drugs, potential future treatments CD was performed, considering articles published from 2012. revised were selected according protocol treatment: evaluation drug association, repositioning research drugs. As result revision, it possible conclude that use benznidazole compounds showed better results when compared as single therapy. search strategy most used pursuing more forms studies focused basic research, is, they pre-clinical stage, using methodologies based vitro animal studies.

Language: Английский

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Drug discovery for chagas disease: A viewpoint

Acta Tropica, Journal Year: 2019, Volume and Issue: 198, P. 105107 - 105107

Published: July 24, 2019

Chagas disease is a neglected tropical caused by the protozoan parasite Trypanosoma cruzi. It significant public health problem, affecting millions of people worldwide. And although it was described 110 years ago, only two old nitroheterocyclic drugs, benznidazole and nifurtimox, are currently available for treatment both have several limitations. Besides clear unmet medical need, many challenges preclude development new treatments, some them related to lack understanding pathophysiology parasite-host interactions. New knowledge tools becoming available, but number chemical entities progressing through preclinical pipeline inadequate. Therefore, still uncertain whether safe, effective accessible drugs will be in near future. The research community must commit even greater collaboration ensure that patients eventually benefit from better treatments.

Language: Английский

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Targeting Cysteine Protease B to Discover Antileishmanial Drugs: Directions and Advances

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117500 - 117500

Published: March 11, 2025

Language: Английский

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Why hasn’t there been more progress in new Chagas disease drug discovery?

Expert Opinion on Drug Discovery, Journal Year: 2019, Volume and Issue: 15(2), P. 145 - 158

Published: Oct. 31, 2019

Introduction: Chagas disease (CD) is a neglected caused by the protozoan parasite Trypanosoma cruzi. In terms of novel drug discovery, there has been no progress since 1960s with same two drugs, benznidazole and nifurtimox, still in use. The complex life cycle, genetic diversity T. cruzi strains, different sensitivities to available as well little interest from pharmaceutical companies inadequate methodologies for translating vitro vivo findings discovery new drugs have all contributed lack progress.Areas covered: this perspective, authors give discussion relevant points connected developments CD provide their expert perspectives.Expert opinion: There are few currently preclinical pipeline treatment CD. Only three classes compounds shown achieve high cure rates mouse models infection: nitroimidazoles (fexinidazole), oxaborole DNDi-6148 proteasome inhibitors (GNF6702). New biomarkers Chagas’ urgently needed diagnosis detection cure/treatment efficacy. Efforts academia more intense interaction accelerate process development necessary.

Language: Английский

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Thiazolidinone/thiazole based hybrids – New class of antitrypanosomal agents

European Journal of Medicinal Chemistry, Journal Year: 2019, Volume and Issue: 174, P. 292 - 308

Published: April 24, 2019

Language: Английский

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Review of pharmacological options for the treatment of Chagas disease

British Journal of Clinical Pharmacology, Journal Year: 2020, Volume and Issue: 88(2), P. 383 - 402

Published: Dec. 14, 2020

Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described century ago, but only two drugs are currently available for treatment: benznidazole (BZN) nifurtimox (NF). Treating CD-infected patients, especially children women of reproductive age, vital order to prevent long-term sequelae, such as heart gastrointestinal dysfunction, this aim still far from being accomplished. Currently, the strongest data support benefit-risk considerations come trials children. Treatment response biomarkers need further development serology questioned best method assess treatment response. This article narrative review on pharmacology CD, particularly BZN NF. Data drug biopharmaceutical characteristics, safety efficacy summarized clinical perspective. Current alternative compounds under evaluation treatment, new possible also discussed. Early diagnosis paediatric an effective safe use (i.e. NF). New urgently needed efficacy, guide efforts academia pharmaceutical companies accelerate process development.

Language: Английский

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Electrochemical Selenation/Cyclization of Quinones: A Rapid, Green and Efficient Access to Functionalized Trypanocidal and Antitumor Compounds

European Journal of Organic Chemistry, Journal Year: 2020, Volume and Issue: 2020(29), P. 4474 - 4486

Published: March 20, 2020

Electrochemical selenation in undivided electrochemical cells allows the preparation of selenium‐containing naphthoquinones. The rapid, green and efficient protocol avoids chemical oxidants enables synthesis target molecules a fast reliable way. This strategy provides general method for quinoidal compounds with activity against five cancer cell lines Trypanosoma cruzi , parasite that causes Chagas disease.

Language: Английский

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Computer-aided design of 1,4-naphthoquinone-based inhibitors targeting cruzain and rhodesain cysteine proteases

Bioorganic & Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 41, P. 116213 - 116213

Published: May 11, 2021

Language: Английский

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Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(5)

Published: March 8, 2024

Abstract A very interesting foundation for this study is the creation of new methods modifying compounds with a 1,2,3‐triazole and chalcone scaffolds, as these are significant in organic synthesis, particularly synthesis bioactive compounds. To contribute to development an efficient method conversion antimicrobial antituberculosis heterocyclics, novel series cyclohepta pyridinone fused 1,2,3‐triazolyl chalcones were designed synthesized. All newly prepared scaffolds characterized by FT‐IR, NMR ( 1 H & 13 C) mass spectrometry. Among tested compounds, hybrids 8b , 8d 8f exhibited exceptional antibacterial susceptibilities zone inhibition 27.84±0.04, 32.27±0.02, 38.26±0.01 mm against E. faecalis bacteria, whereas had better antitubercular potency M. tuberculosis 37 Rv strain MIC value 5.25 μg/mL, compared Streptomycin [MIC=5.01 μg/mL]. synthesized initially assessed silico targeted protein i. e., DprE1 that indicated compound 8d, 8h along several other possible inhibitors. Based on docking results, showed amino acids His 74 (A), Lys 76 Cys 332 Asp 331 Val 307 Tyr 357 Met 226 Gln 276 Gly 75 Peo 58 Leu 259 309 (A) highly stable binding receptor Mycobacterium (PDB: 4G3 U). Moreover, physicochemical characteristics, filtration molecular properties, assessment toxicity, bioactivity scores relation ADME (absorption, distribution, metabolism, excretion).

Language: Английский

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Multifunctional organometallic compounds for the treatment of Chagas disease: Re(i) tricarbonyl compounds with two different bioactive ligands

Dalton Transactions, Journal Year: 2023, Volume and Issue: 52(6), P. 1623 - 1641

Published: Jan. 1, 2023

Chagas' disease (American Trypanosomiasis) is an ancient and endemic illness in Latin America caused by the protozoan parasite Trypanosoma cruzi. Although there urgent need for more efficient less toxic chemotherapeutics, no new drugs to treat this have entered clinic last decades. Searching metal-based prospective antichagasic drugs, work, multifunctional Re(I) tricarbonyl compounds bearing two different bioactive ligands were designed: a polypyridyl NN derivative of 1,10-phenanthroline monodentate azole (Clotrimazole CTZ or Ketoconazol KTZ). Five fac-[Re(CO)3(NN)(CTZ)](PF6) fac-[Re(CO)3(NN)(KTZ)](PF6) synthesized fully characterized. They showed activity against epimastigotes (IC50 3.48-9.42 μM) trypomastigotes T. cruzi 0.61-2.79 moderate good selectivity towards compared VERO mammalian cell model. In order unravel mechanism action our compounds, potential targets experimentally theoretically studied, namely DNA one enzymes involved ergosterol biosynthetic pathway, CYP51 (lanosterol 14-α-demethylase). As hypothesized, shared vitro similar mode as that disclosed single moieties included chemical entities. Additionally, relevant physicochemical properties biological interest drug development, lipophilicity stability solution media, determined. The whole set results demonstrates potentiality these tricarbonyls promising candidates further antitrypanosomal development.

Language: Английский

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