The latest progress in assay development in leishmaniasis drug discovery: a review of the available papers on PubMed from the past year.

Introduction: Leishmaniasis is a significant neglected tropical disease with limited treatment options that urgently requires ongoing efforts in drug discovery. Recent advances have focused on the development of new assays and methods to identify effective therapeutic candidates.

Areas Covered: This review explores recent trends and methodologies in leishmaniasis drug discovery, with a particular focus on in silico and in vitro studies, as well as in vivo validation, using animal models.

Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection.

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups.

Anti- screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice.

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti- activity and identify promising candidates for further evaluation.

Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice.

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T.

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against .

is a protozoan that infects up to a third of the world's population. This parasite can cause serious problems, especially if a woman is infected during pregnancy, when toxoplasmosis can cause miscarriage, or serious complications to the baby, or in an immunocompromised person, when the infection can possibly affect the patient's eyes or brain. To identify potential drug candidates that could counter toxoplasmosis, we selected 13 compounds which were pre-screened in silico based on the proteome of to be evaluated in vitro against the parasite in a cell-based assay.

Laboratory Diagnosis of Cutaneous and Visceral Leishmaniasis: Current and Future Methods.

Leishmaniasis is a neglected tropical disease with two main clinical forms: cutaneous and visceral leishmaniasis. Diagnosis of leishmaniasis is still a challenge, concerning the detection and correct identification of the species of the parasite, mainly in endemic areas where the absence of appropriate resources is still a problem. Most accessible methods for diagnosis, particularly in these areas, do not include the identification of each one of more than 20 species responsible for the disease.

Repurposing topical triclosan for cutaneous leishmaniasis: Preclinical efficacy in a murine Leishmania (L.) amazonensis model.

Leishmaniasis remains an important neglected tropical infection caused by the protozoan Leishmania and affects 12 million people in 98 countries. The treatment is limited with severe adverse effects. In the search for new therapies, the drug repositioning and combination therapy have been successfully applied to neglected diseases.

The preclinical discovery and development of oral miltefosine for the treatment of visceral leishmaniasis: a case history.

Introduction: Visceral leishmaniasis (VL) is a vector-borne disease caused by or . Closely related to poverty, VL is fatal and represents one of the main burdens on public health in developing countries. Treatment of VL relies exclusively on chemotherapy, a strategy still experiencing numerous limitations.

Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi.

Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neolignans from Nectandra leucantha (Lauraceae).

Topical tamoxifen in the therapy of cutaneous leishmaniasis.

The aims of the present work were to test the effect of tamoxifen administered topically and the therapeutic efficacy of tamoxifen and pentavalent antimonial combinations in an experimental model of cutaneous leishmaniasis. BALB/c mice infected with a luciferase expressing line of Leishmania amazonensis were treated with topical tamoxifen in two different formulations (ethanol or oil-free cream) as monotherapy or in co-administration with pentavalent antimonial. Treatment efficacy was evaluated by lesion size and parasite burden, quantified through luminescence, at the end of treatment and 4 weeks later.

A Luciferase-Expressing Leishmania braziliensis Line That Leads to Sustained Skin Lesions in BALB/c Mice and Allows Monitoring of Miltefosine Treatment Outcome.

Background: Leishmania braziliensis is the most prevalent species isolated from patients displaying cutaneous and muco-cutaneous leishmaniasis in South America. However, there are difficulties for studying L. braziliensis pathogenesis or response to chemotherapy in vivo due to the natural resistance of most mouse strains to infection with these parasites.

Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism of Leishmania (L.) infantum.

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether the in vitro anti-Leishmania infantum and anti-Trypanosoma cruzi activities of this therapeutic class would be shared by other non-dihydropyridine-CCBs.

Efficacy of tamoxifen and miltefosine combined therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis.

Objectives: The objective of this study was to characterize in vitro interactions and evaluate the antileishmanial activity of tamoxifen and miltefosine combinations.

Methods: Interactions between drugs were evaluated in vitro against Leishmania amazonensis promastigotes and intracellular amastigotes by a modified isobologram method. Four different drug ratios were used to calculate the FIC index (FICI) and the mean sum of FICI.

Antileishmanial activity of the estrogen receptor modulator raloxifene.

Background: The treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects. Additionally, parasite resistance in the treatment of leishmaniasis has been demonstrated for the majority of drugs available, making the search for more effective and less toxic drugs and treatment regimens a priority for the control of leishmaniasis. The aims of this study were to evaluate the antileishmanial activity of raloxifene in vitro and in vivo and to investigate its mechanism of action against Leishmania amazonensis.

Combination therapy with tamoxifen and amphotericin B in experimental cutaneous leishmaniasis.

Leishmaniasis chemotherapy remains very challenging. The high cost of active drugs, along with the severity of their side effects and the increasing failure rate of the current therapeutic schemes, calls for the discovery of new active drugs and schemes of treatment. The use of combination therapy has gained much attention in recent years as a possible strategy for overcoming the various shortcomings in the present arsenal.

Combination therapy with nitazoxanide and amphotericin B, Glucantime®, miltefosine and sitamaquine against Leishmania (Leishmania) infantum intracellular amastigotes.

Leishmaniasis is a neglected disease that affects poorest population mainly in developing countries, representing one of the major causes of mortality and morbidity. Therefore, efforts to find new chemotherapeutics for leishmaniasis remain a priority. Previous reports demonstrated the in vitro and in vivo antileishmanial activity of nitazoxanide, an antiprotozoan agent used in the treatment of infectious diarrhea.

Parasite burden in Leishmania (Leishmania) amazonensis-infected mice: validation of luciferase as a quantitative tool.

Given the lack of effective and safe alternatives to the drugs already in use, considerable efforts are being applied to the search of new therapeutic options to treat leishmaniasis. A necessary step in the discovery of antileishmanial drugs is the validation of drug candidates in mouse models. The standard methods to quantify the parasite burden in animal models, mainly culture-based, are time consuming and expensive.

Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi.

The objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi-infected hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L.

Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs.

The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime.

In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae).

Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. In this work, the CH(2)Cl(2) phase from MeOH extract from the leaves of Baccharis retusa DC.

Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae).

Leishmaniasis, Chagas disease, and malaria affect the poorest population around the world, with an elevated mortality and morbidity. In addition, the therapeutic alternatives are usually toxic or ineffective drugs especially those against the trypanosomatids. In the course of selection of new anti-protozoal compounds from Brazilian flora, the CH(2)C(l2) phase from MeOH extract obtained from the leaves of Pentacalia desiderabilis (Vell.

In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: detection of viable Leishmania (L.) chagasi by real-time PCR.

The need for novel and efficacious drugs against neglected parasitic diseases, such as Leishmaniasis and American Trypanosomiasis, is certainly apparent. In this work, we evaluated the in vitro potential of the calcium channel blocker bepridil against Leishmania spp. and Trypanosoma cruzi parasites and exploited an experimental assay using a hamster model with Leishmania (L.