Recent progress in drug targets and inhibitors towards combating leishmaniasis

Vijayakumar, Saravanan; Das, Pradeep

doi:10.1016/j.actatropica.2018.02.010

Cited by 57 publications

(22 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Results showed that the flavonoidpresented an effective antileishmanial action in vitro, low toxicity to murine cells and, most importantly, the ability to control L infantum infection in vivo. Miltefosine was used as a well-characterized control drug 46,47. All in all, results suggested that CMt displayed similar immunological and parasitological effects to those obtained when miltefosine was used, mainly when the flavonoid was incorporated into micelles as its delivery system.Initially, antileishmanial action of CMt against L amazonensis and L infantum species was analysed in vitro.…”

mentioning

confidence: 83%

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Pereira

Mendonça

Tavares

et al. 2020

Parasite Immunology

View full text Add to dashboard Cite

Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4'-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune How to cite this article: Pereira IAG, Mendonça DVC, Tavares GSV, et al. Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis.

show abstract

mentioning

confidence: 83%

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Pereira

Mendonça

Tavares

et al. 2020

Parasite Immunology

View full text Add to dashboard Cite

show abstract

“…En este mismo ambiente, conceptualmente, los inhibidores se definen como moléculas capaces de enlazarse a un objetivo específico bloqueando su actividad. En cuanto a los blancos moleculares de enfermedades desatendidas, los criterios básicos para la selección de los mismos son que se presenten prioritariamente en el agente etiológico y que se expresen en la etapa de vida patógena para el huésped (8). Aunque la inversión en investigación y desarrollo farmacéutico ha aumentado substancialmente, la falta de un aumento correspondiente en la identificación de nuevas moléculas con aprobación para terapéutica, indica que la innovación farmacéutica sigue siendo un desafío para los grupos de investigación (9).…”

Section: Nuevos Enfoques Terapéuticos Y Blancos Moleculares En Tripanunclassified

“…Como ya ha sido mencionado, entre los principales criterios para la validación de un blanco molecular se encuentra que el mismo sea crucial para el metabolismo del patógeno, prefiriéndose si está presente exclusivamente en el parásito. Sin embargo, algunos fármacos no siguen este patrón, derivando en los efectos adversos y la baja eficiencia (8). Entre los blancos más estudiados presentes en esta familia de parásitos, las enzimas del metabolismo tiol-dependiente son consideradas entre las más prometedoras (7,10).…”

Section: Nuevos Enfoques Terapéuticos Y Blancos Moleculares En Tripanunclassified

Leishmaniasis y Enfermedad de Chagas: Herramientas para Nuevos Enfoques en su Tratamiento

Garay

Diaz

Kayano

et al. 2019

Rev. Soc. cient. Parag.

View full text Add to dashboard Cite

La Leishmaniasis y la Enfermedad de Chagas afectan a millones de personas en América Latina y en otras regiones del mundo, siendo las poblaciones rurales pobres y vulnerables las más afectadas. Aunque se han realizado esfuerzos conjuntos para el combate de estas enfermedades desatendidas, la combinación de diferentes factores como el tratamiento ineficiente, la falta de interés para invertir en la búsqueda de nuevas fuentes terapéuticas y el surgimiento de cepas de parásitos resistentes acaban complicando las perspectivas. Esta situación torna de vital importancia el desarrollo de nuevas estrategias que apunten a la identificación de moléculas con potencial aplicación en la terapia o que puedan ejercer un efecto sinérgico cuando se complementan con la quimioterapia actual. Uno de los enfoques propuestos para este fin consiste en la búsqueda de estos agentes basados en blancos farmacológicos presentes en los parásitos causantes de las citadas enfermedades. Entre estos blancos moleculares se encuentran las enzimas implicadas en vías esenciales del parásito, como la Tripanotiona Reductasa (TR), involucrada en el combate al estrés oxidativo generado por las especies reactivas de oxígeno producidas por macrófagos del huésped durante la infección. Una herramienta importante en la búsqueda de inhibidores para esta enzima puede ser encontrada a través de la aplicación de herramientas in silico, que resulta un método relativamente rápido y de bajo costo, el cual permite seleccionar moléculas con potencial a partir de una gran variedad de fuentes. Los ensayos basados en el tamizaje (“screening”) virtual permiten la selección de moléculas de forma racional, que mediante ensayos complementarios pueden dar lugar al surgimiento futuro de nuevos fármacos.

show abstract

“…Efforts were made in the past to identify a lot of small-molecule inhibitors against leishmaniasis [ 26 ]. However, the number of well-established drug targets for VL is limited [ 27 ]. Hence, identifying new drug target(s) becomes a constant requirement in the process of combating VL.…”

Section: Introductionmentioning

confidence: 99%

Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

2020

Self Cite

View full text Add to dashboard Cite

High-throughput proteomic technologies are widely used for understanding the disease mechanism, drug-resistant mechanism, and to identify drug targets and markers for diagnostics. Studies with proteomics applications, relating to Leishmaniasis, are being constantly reported in the literature. However, from such studies, a readily accessible knowledge of differentially modulated proteins associated with Leishmaniasis is lacking. Hence, we performed a systematic review concerning differentially modulated proteins (DMP) in Leishmania as well as host infected with Leishmania from the published articles between the years 2000 and 2019. This review is classified into five different sections, namely, DMP in the host after Leishmania infection, DMP between different strains of Leishmania , DMP in drug-resistant Leishmania , DMP in Leishmania under stress, and DMP in different life stages of Leishmania. A lot of consensuses could be observed among the DMP in drug-resistant and stressed Leishmania . In addition to the review, a database was constructed with the data collected in this study (protein accession ID, protein name, gene name, host organism, experimental conditions, fold change, and regulatory data). A total of 2635 records are available in the database. We believe this review and the database will help the researcher in understanding the disease better and provide information for the targeted proteomics study related to Leishmaniasis. Database availability: http://ldepdb.biomedinformri.com/ . Electronic supplementary material The online version of this article (10.1007/s11033-020-05936-z) contains supplementary material, which is available to authorized users.

show abstract

Recent progress in drug targets and inhibitors towards combating leishmaniasis

Cited by 57 publications

References 113 publications

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis

Leishmaniasis y Enfermedad de Chagas: Herramientas para Nuevos Enfoques en su Tratamiento

Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

Contact Info

Product

Resources

About