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.

Selective Activity Against Amastigote Forms of Trypanosoma cruzi and Leishmania infantum of Diastereomeric Dicentrine N-oxides.

As part of our continuous research for the discovery of bioactive compounds against Trypanosoma cruzi and Leishmania infantum, the alkaloid (6aS)-dicentrine (1) was oxidized to afford (6aS,6S)- (2) and (6aS,6R)- (3) dicentrine-N-oxides. Evaluation of the cytotoxicity against NCTC cells indicated that 2 and 3 are non-toxic (CC>200 μM) whereas 1 demonstrated CC of 52.0 μM.

Mitochondrial Imbalance of Induced by the Marine Alkaloid 6-Bromo-2'-de--Methylaplysinopsin.

Chagas disease, caused by , affects seven million people worldwide and lacks effective treatments. Using bioactivity-guided fractionation, NMR, and electrospray ionization-high resolution mass spectrometry (ESI-HRMS) spectral analysis, the indole alkaloid 6-bromo-2'-de--methylaplysinopsin () was isolated and chemically characterized from the marine coral . was tested against trypomastigotes and intracellular amastigotes of , resulting in IC values of 62 and 5.

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.

Antileishmanial Effects of Acetylene Acetogenins from Seeds of (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives.

As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (,,)-3-hydroxy-4-methyl-2-(-eicos-11'-yn-19'-enyl)butanolide () and (,,)-3-hydroxy-4-methyl-2-(-eicos-11'-ynyl)butanolide (), from the seeds of (Warm.) R.E.

Optimization of physicochemical properties is a strategy to improve drug-likeness associated with activity: Novel active and selective compounds against Trypanosoma cruzi.

Trypanosoma cruzi is the causing agent of Chagas disease, a parasitic infection without efficient treatment for chronic patients. Despite the efforts, no new drugs have been approved for this disease in the last 60 years. Molecular modifications based on a natural product led to the development of a series of compounds (LINS03 series) with promising antitrypanosomal activity, however previous chemometric analysis revealed a significant impact of excessive lipophilicity and low aqueous solubility on potency of amine and amide derivatives.

Synthesis and Structure-Activity Relationship of Dehydrodieugenol B Neolignans against .

is the etiologic agent of Chagas disease, which affects over seven million people, especially in developing countries. Undesirable side effects are frequently associated with current therapies, which are typically ineffective in the treatment of all stages of the disease. Here, we report the first synthesis of the neolignan dehydrodieugenol B, a natural product recently shown to exhibit activity against .

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.

Calanolides E1 and E2, two related coumarins from Cambess. (Clusiaceae), displayed activity against amastigote forms of and .

In the present work, the MeOH extract from stem barks of Cambess. (Clusiaceae) displayed activity against amastigote forms of and and was subjected to a bioactivity-guided fractionation to give two related coumarins - calanolides E1 () and E2 (). Compounds and were actives to with EC values of 12.

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.

Antitrypanosomal activity of isololiolide isolated from the marine hydroid Macrorhynchia philippina (Cnidaria, Hydrozoa).

Marine invertebrates are a rich source of small antiparasitic compounds. Among them, Macrorhynchia philippina is a chemically underexplored marine cnidarian. In the search for candidates against the neglected protozoan Chagas disease, we performed a bio-guided fractionation to obtain active compounds.

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.