Progress in antileishmanial drugs: Mechanisms, challenges, and prospects

PLoS neglected tropical diseases, Journal Year: 2025, Volume and Issue: 19(1), P. e0012735 - e0012735

Published: Jan. 3, 2025

Leishmaniasis, a neglected tropical disease caused by Leishmania parasites, continues to pose global health challenges. Current treatments face issues like resistance, safety, efficacy, and cost. This review covers the discovery, mechanisms of action, clinical applications, limitations key antileishmanial agents: pentavalent antimonials, amphotericin B, miltefosine, paromomycin, pentamidine. Despite toxicity resistance (antimonials), hospitalization needs side effects (amphotericin B), regional efficacy variability (miltefosine), inconsistent outcomes (paromomycin), severe (pentamidine), these drugs are vital. Novel strategies overcome deficiencies current therapies highlighted, including combination regimens, advanced drug delivery systems, immunomodulatory approaches. Comprehensive cooperative efforts crucial fully realize potential advancements in pharmacotherapy reduce unacceptable worldwide burden imposed this disease.

Language: Английский

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Visceral leishmaniasis: a global overview

Journal of Global Health Science, Journal Year: 2020, Volume and Issue: 2(1)

Published: Jan. 1, 2020

Language: Английский

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An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

Molecules, Journal Year: 2021, Volume and Issue: 26(15), P. 4629 - 4629

Published: July 30, 2021

The protozoan diseases Human African Trypanosomiasis (HAT), Chagas disease (CD), and leishmaniases span worldwide therefore their impact is a universal concern. present regimen against kinetoplastid infections poor insufficient. Target-based design expands the horizon of drug development offers novel chemical entities potential candidates to therapeutic arsenal aforementioned neglected diseases. In this review, we report most promising targets main parasites, as well corresponding inhibitors. This overview part Special Issue, entitled “Advances Medicinal Chemistry Kinetoplastid Protozoa (Trypanosoma brucei, Trypanosoma cruzi Leishmania spp.) Infections: Drug Design, Synthesis Pharmacology”.

Language: Английский

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Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Leishmaniasis, which is caused by a parasitic protozoan of the genus Leishmania, still major threat to global health, impacting millions individuals worldwide in endemic areas. Chemotherapy has been principal method for managing leishmaniasis; nevertheless, evolution drug resistance offers significant obstacle therapeutic success. Drug-resistant behavior these parasites complex phenomenon including both innate and acquired mechanisms. Resistance frequently related changes transportation, target alterations, enhanced efflux from pathogen. This review revealed specific genetic mutations Leishmania that are associated with commonly used antileishmanial drugs such as pentavalent antimonials, miltefosine, amphotericin B, paromomycin, resulting gene expression along functioning various proteins involved uptake, metabolism, efflux. Understanding linked essential creating approaches tackling avoiding spread drug-resistant variants. Based on treatments focus pathways could potentially improve treatment efficacy help long-term leishmaniasis control. More study needed uncover complete range generating medication develop new therapies based available information.

Language: Английский

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Synthesis and in vitro antiprotozoal evaluation of novel Knoevenagel hydroxychloroquine derivatives

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Leishmaniasis and Chagas diseases affect millions of people, particularly in developing countries, with conventional treatments proving unsatisfactory due to increasing drug resistance high toxicity. Therefore, there is an urgent need for new drugs combat neglected tropical (NTDs). In this study, we synthesized 15 Knoevenagel adducts derived from hydroxychloroquine evaluated their antiprotozoal activity against Leishmania infantum, L. amazonensis, Trypanosoma cruzi. The exhibited low toxicity epithelial LLC-MK2 cells J774A.1 macrophages. meta- para-chloro benzaldehyde demonstrated T. cruzi epimastigotes, though a lower selective index (SI) compared the standard benznidazole. However, isovaleraldehyde ortho-, meta-, showed SI values ranging 10.97 8.11 similar amphotericin B (AmpB, = 9.37), no statistically significant difference (p > 0.05). These same compounds inhibited infantum promastigotes, but less AmpB. results suggest that may serve as antileishmanial agents.

Language: Английский

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Exploring Lamiaceae diterpenoids as potential multitarget therapeutics for leishmaniasis and chagas disease

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Language: Английский

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Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria

Natural Product Reports, Journal Year: 2021, Volume and Issue: 38(12), P. 2214 - 2235

Published: Jan. 1, 2021

This Review discusses the isolation and bioactivity of marine alkaloids against protozoan parasite diseases, chemical syntheses that enable further development these scaffolds as drug leads.

Language: Английский

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Facing diseases caused by trypanosomatid parasites: rational design of multifunctional oxidovanadium(IV) complexes with bioactive ligands

Frontiers in Chemical Biology, Journal Year: 2024, Volume and Issue: 2

Published: Jan. 16, 2024

Searching for new prospective drugs against Chagas disease (American trypanosomiasis) and Leishmaniasis, a series of five heteroleptic vanadium compounds, [V IV O(L-H)(mpo)], where L are 8-hydroxyquinoline derivatives mpo is 2-mercaptopyridine N -oxide, synthesized characterized. Comprehensive characterizations conducted in solid state solution. The compounds evaluated on epimastigotes trypomastigotes Trypanosoma cruzi promastigotes Leishmania infantum , alongside VERO cells, as mammalian cell model. exhibit activity both forms T. L. with the trypomastigote infective stage displaying highest sensitivity. most selective compound O(L2-H)(mpo)], L2 = 5-chloro-7-iodo-8-hydroxyquinoline, globally shows adequate selectivity towards parasite was selected to carry out further in-depth biological studies. O(L2-H)(mpo)] significantly impacted infection potential cell-derived hindered replication amastigote form. Low total uptake by parasites preferential accumulation soluble proteins fraction, negligible localization DNA determined. A trypanocide effect observed across various concentrations compound. generation oxidative stress induction mitochondria-dependent apoptosis proposed main mechanisms parasite’s death V O compounds. Both theoretical predictions experimental data support hypothesis that inhibiting parasite-specific enzyme NADH-fumarate reductase plays crucial role trypanocidal action these complexes. Globally, O(L-H)(mpo)] complexes could be considered interesting anti- agents deserve research.

Language: Английский

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Neglected tropical diseases in Brazil: lack of correlation between disease burden, research funding and output

Tropical Medicine & International Health, Journal Year: 2020, Volume and Issue: 25(11), P. 1373 - 1384

Published: Aug. 29, 2020

To assess the correlation between burden of seven priority neglected tropical diseases (NTDs) included in Brazilian National Agenda Priorities Health Research - tuberculosis, Chagas disease, leprosy, malaria, leishmaniasis, dengue and schistosomiasis their respective research funding output.This retrospective review obtained data on disease from Global Burden Disease Study open access sources. Publications were retrieved Scopus SciELO, characterised according to type conducted. Correlation funding, output was assessed by comparing 'expected' 'observed' values for publications relative proportional each disease.There an emphasis basic biomedical (average 30% publications) a shortage health policy systems 7%) social sciences 3%). poorly correlated with burden. Tuberculosis, accounted more than 75% total NTD-related DALYs, but only 34% publications. Leprosy, leishmaniasis together, received 49% despite being responsible 9% DALYs.The analysis evidenced lack burden, government NTDs Brazil. Our findings highlight importance monitoring needs, investments outputs inform optimise uptake evidence action, particularly developing countries, where resources are scarce capacity is limited. The results contribute highlighting need improving coordination scientific activities public needs effective impact.Evaluer la corrélation entre charge de sept maladies tropicales négligées (MTN) prioritaires incluses dans le programme national brésilien des priorités en matière recherche santé tuberculose, maladie Chagas, lèpre, paludisme, leishmaniose, et schistosomiase leurs financements respectifs les résultats. MÉTHODES: Cette revue rétrospective obtenu données sur morbidité l'étude Charge Globale Maladies financement provenant sources accès publique. Les ont été extraites SciELO caractérisées selon menée. La financement, résultats évaluée comparant valeurs “attendues” “observées” pour par rapport à proportionnel chaque maladie. RÉSULTATS: L'accent mis biomédicale fondamentale (en moyenne une pénurie politiques systèmes sociales étaient mal associés morbidité. représentaient plus du EVCI, mais ne que leishmaniose ensemble, reçu liés aux MTN alors qu'ils n'étaient responsables EVCI.L’analyse évidence absence morbidité, résultat plupart MTN. Nos soulignent l'importance suivi besoins santé, investissements éclairer optimiser l'utilisation l'action, particulier pays développement, où ressources sont rares capacité est limitée. contribuent politique soulignant nécessité d'améliorer planification stratégique activités scientifiques un impact efficace.

Language: Английский

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Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

Molecules, Journal Year: 2022, Volume and Issue: 27(1), P. 319 - 319

Published: Jan. 5, 2022

Human protozoan diseases represent a serious health problem worldwide, affecting mainly people in social and economic vulnerability. These have attracted little investment drug discovery, which is reflected the limited available therapeutic arsenal. Authorized drugs present problems such as low efficacy some stages of disease or toxicity, result undesirable side effects treatment abandonment. Moreover, emergence drug-resistant parasite strains makes necessary an even greater effort to develop safe effective antiparasitic agents. Among chemotypes investigated for parasitic diseases, indole nucleus has emerged privileged molecular scaffold generation new candidates. In this review, authors provide overview indole-based compounds developed against important namely malaria, trypanosomiasis leishmaniasis, by focusing on design, optimization synthesis most relevant synthetic scaffolds recently reported.

Language: Английский

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