Mechanistic Insights and Therapeutic Potential of the Antidepressant Amitriptyline against .

Leishmaniasis remains a significant global health challenge, with limited therapeutic options and rising drug resistance. The repurposing of Food and Drug Administration approved antidepressants as amitriptyline, a widely used tricyclic drug, could offer a promising strategy for developing novel antileishmanial agents. This study investigates the in vitro activity of amitriptyline against promastigotes and intracellular amastigotes and explores its ultrastructural effects and potential in combination therapy.

Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.

The problems with current strategies to control canine visceral Leishmaniasis (CVL), which include the euthanasia of infected animals, and also the toxicity of the drugs currently used in human treatments for CVL, add urgency to the search for new therapeutic agents. This study aimed to evaluate the activity against of 12 amides that are chemically inspired by gibbilimbol B, a bioactive natural product that was initially obtained from . Three of these compounds--(2-ethylhexyl)-4-chlorobenzamide (), -(2-ethylhexyl)-4-nitrobenzamide (), and -(2-ethylhexyl)-4-(-butyl)benzamide () -demonstrated activity against the intracellular amastigotes without toxicity to mammalian host cells (CC > 200 μM); compounds , , and resulted in EC values of 12.

In Vitro and In Silico Evaluation of the Leishmanicidal and Trypanocidal Activities of Lignan Methylpiperitol Isolated from Persea Fulva.

Neglected Tropical Diseases are a significant concern as they encompass various infections caused by pathogens prevalent in tropical regions. The limited and often highly toxic treatment options for these diseases necessitate the exploration of new therapeutic candidates. In the present study, the lignan methylpiperitol was isolated after several chromatographic steps from Persea fulva L.

Steam distillation, supercritical fluid extraction, and anti- activity of compounds from pink pepper ( Raddi).

Anti- activity of compounds from fruits of Raddi (pink pepper) were evaluated, using sustainable techniques such as steam distillation (SD) and supercritical fluid extraction (SFE). SD was optimised using a design of experiment and SFE was carried out using supercritical CO solvent (300 bar and 60 °C). Results of the anti- activity showed that the essential oil presented high activity (IC = 4.

Saturated Iso-Type Fatty Acids from the Marine Bacterium with Anti-Trypanosomal Potential.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, , , and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-, , , , and To conduct this study, EtOAc extracts were prepared and tested against The crude extracts showed IC values ranging from 15 to 51 μg/mL against the trypomastigotes.

Andrographolide: A Diterpenoid from Identified as a New Hit Compound against Using Machine Learning and Experimental Approaches.

American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti- potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates.

Effect of partial O-methylation in dehydrodieugenol on its antitrypanosomal activity - correlation with the toxicity using cell membrane models.

Biseugenol (1), a neolignan with antiprotozoal activity against Trypanosoma cruzi, was partially methylated, and the compound obtained - methyl biseugenol (2) - had its activity evaluated against the extracellular (trypomastigotes) and intracellular (amastigotes) forms of T. cruzi. It was observed that both compounds 1 and 2 exhibited similar effects against trypomastigotes (IC of 11.

Identification of inhibitors as drug candidates against Chagas disease.

Chagas disease, after more than a century after its discovery, is still a major public health problem. It is estimated that approximately 10 million people worldwide are infected with T. cruzi.

The Potential of Secondary Metabolites from Plants as Drugs or Leads against -An Update from 2012 to 2021.

Background: Chagas disease (American Trypanosomiasis) is classified by the World Health Organization (WHO) as one of the seventeen neglected tropical diseases (NTD), affecting, mainly, several regions of Latin America.

Introduction: However, immigration has expanded the range of this disease to other continents. Thousands of patients with Chagas disease die annually, yet no new therapeutics for Chagas disease have been approved, with only nifurtimox and benznidazole available.

A new reduced chalcone-derivative affects the membrane permeability and electric potential of multidrug-resistant Enterococcusfaecalis.

The emergence and spread of multidrug-resistant (MDR) enterococci and other Gram-positive bacteria represents a severe problem due to the lack of effective therapeutic alternatives. Natural products have long been an important source of new antibacterial scaffolds and can play a key role in the current antibiotic crisis. Enterococci are predominantly non-pathogenic gastrointestinal commensal bacteria, but among them, Enterococcus faecalis and Enterococcus faecium represent the species that account for most clinically relevant infections.

Evaluation of antileishmanial potential of the antidepressant escitalopram in Leishmania infantum.

Neglected tropical diseases (NTDs) such as visceral leishmaniasis (VL) present a limited and toxic therapeutic arsenal, and drug repositioning represents a safe and cost-effective approach. In this work, we investigated the antileishmanial potential and the mechanism of lethal action of the antidepressant escitalopram. The efficacy of escitalopram was determined ex-vivo using the intracellular Leishmania (L.

Bioenergetics impairment of Trypanosoma cruzi by the antihypertensive manidipine: A drug repurposing strategy.

Considering the lack of effective and safe therapy for the treatment of Chagas disease, the antihypertensive drug manidipine (MDP) was in vitro evaluated against Trypanosoma cruzi. The bioenergetics of trypomastigotes was studied in the presence of the drug using fluorimetric and luminescent assays. Manidipine showed a potent antiparasitic activity, with IC values of 0.

Targeting intracellular Leishmania (L.) infantum with nitazoxanide entrapped into phosphatidylserine-nanoliposomes: An experimental study.

Leishmaniasis is a parasitic neglected tropical disease and result in a broad spectrum of clinical manifestations, ranging from a single ulceration to a progressive and fatal visceral disease. Comprising a limited and highly toxic therapeutic arsenal, new treatments are urgently needed. Targeting delivery of drugs has been a promising approach for visceral leishmaniasis (VL).

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.

Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity.

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB).

Sertraline Delivered in Phosphatidylserine Liposomes Is Effective in an Experimental Model of Visceral Leishmaniasis.

Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. (L.) parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment.

Electrospray mass-spectrometry guided target isolation of neolignans from Nectandra leucantha (Lauraceae) by high performance- and spiral-coil countercurrent chromatography.

Nectandra leucantha (Lauraceae) is a tree indigenous to the tropical Atlantic forests of Brazil, one of the most biodiverse flora hotspots worldwide. This plant species contains high concentrations of neolignan and dehydrodieugenol derivatives that express significant in-vitro activities against various parasite strains. These activities are however responsible for severe tropical human infections, such as Leishmaniasis (Leishmania spp.

Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum.

Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids.

Antitrypanosomal activity of epi-polygodial from Drimys brasiliensis and its effects in cellular membrane models at the air-water interface.

Epi-polygodial, a drimane sesquiterpene was isolated from Drimys brasiliensis (Winteraceae). This compound demonstrated high parasite selectivity towards Trypanosoma cruzi trypomastigotes (IC = 5.01 μM) with a selectivity index higher than 40.

Efficacy of sertraline against : an in vitro and in silico study.

Background: Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease.

Methods: In this work, we studied the activity of the antidepressant drug sertraline against trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches.

Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both strains inside different host cells, including cardiomyocytes, with IC values between 1 to 10 μM, and activity against bloodstream trypomastigotes, with IC of 14 μM.

Pharmacokinetic of meglumine antimoniate encapsulated in phosphatidylserine-liposomes in mice model: A candidate formulation for visceral leishmaniasis.

Visceral leishmaniasis (VL) is a fatal parasitic disease caused by the protozoan Leishmania spp. Meglumine antimoniate (MA) is the main treatment and has demonstrated a promising efficacy in a VL-model when encapsulated into negatively charged liposomes. Considering the current concept for the evaluation of pharmacokinetic parameters at early phases of drug discovery, we developed a formulation of MA-encapsulated into phosphatidylserine liposomes (MA-LP) and analyzed the in vitro antileishmanial activity, physicochemical properties, and pharmacokinetic profile in a mice model.

Ergosterol isolated from the basidiomycete affects plasma membrane and mitochondria.

Background: Major drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom in the search for potential antiparasitic compounds.