A5011623267- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Synthesis and Biological Evaluation
- Traditional and Medicinal Uses of Annonaceae
- Essential Oils and Antimicrobial Activity
- Microbial Natural Products and Biosynthesis
- Natural product bioactivities and synthesis
- Computational Drug Discovery Methods
- Bioactive Compounds and Antitumor Agents
- Malaria Research and Control
- Toxin Mechanisms and Immunotoxins
- Phytochemical compounds biological activities
- Antifungal resistance and susceptibility
- Phosphodiesterase function and regulation
- Plant biochemistry and biosynthesis
- Natural Compound Pharmacology Studies
- Ethnobotanical and Medicinal Plants Studies
- Bioactive natural compounds
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Cholinesterase and Neurodegenerative Diseases
- Quinazolinone synthesis and applications
- Pharmacogenetics and Drug Metabolism
- Parasites and Host Interactions
- Biological and pharmacological studies of plants
University of Antwerp
2015-2024
Provincial Institute for Hygiene
2021
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand libraries can access far greater space, provided that the predictive accuracy sufficient useful Through largest and most diverse virtual HTS campaign reported date, comprising 318 individual projects, we demonstrate our AtomNet® convolutional neural network...
Abstract Background Worldwide particularly in developing countries, a large proportion of the population is at risk for tropical parasitic diseases. Several medicinal plants are still used traditionally against protozoal infections Yemen and Saudi Arabia. Thus present study investigated vitro antiprotozoal activity twenty-five collected from Arabian Peninsula. Methods Plant materials were extracted with methanol screened erythrocytic schizonts Plasmodium falciparum , intracellular...
The present study investigated the in vitro antiprotozoal activity of sixteen selected medicinal plants. Plant materials were extracted with methanol and screened against erythrocytic schizonts Plasmodium falciparum, intracellular amastigotes Leishmania infantum Trypanosoma cruzi free trypomastigotes T. brucei. Cytotoxic was determined MRC-5 cells to assess selectivity. criterion for an IC₅₀ < 10 μg/mL (<5 brucei) a selectivity index ≥4. Antiplasmodial found extracts Prosopis juliflora...
Visceral leishmaniasis is a severe parasitic disease that one of the most neglected tropical diseases. Treatment options are limited, and there an urgent need for new therapeutic agents. Following HTS campaign hit optimization, novel series amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound 26 shows high levels vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof concept this series.
New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field urgently required. Despite concerted efforts over last several years, number of new chemical entities suitable clinical development treatment Leishmania remains low. Here, we describe discovery preclinical DNDI-6174, an inhibitor cytochrome bc 1 complex activity originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required...
Reverse hydroxamate-based inhibitors of IspC, a key enzyme the non-mevalonate pathway isoprenoid biosynthesis and validated antimalarial target, were synthesized biologically evaluated. The binding mode one derivative in complex with EcIspC divalent metal ion was clarified by X-ray analysis. Pilot experiments have demonstrated vivo potential.
New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library 10,000 drug-like compounds against 7 disease pathogens resulted in an integrated dataset 744 hits. We discuss prioritization these hits each pathogen and strong correlation observed between active more than two mammalian cell toxicity. Our work suggests efficiency early drug discovery diseases can be enhanced through collaborative, multi-pathogen approach.
Several trypanosomatid cyclic nucleotide phosphodiesterases (PDEs) possess a unique, parasite-specific cavity near the ligand-binding region that is referred to as P-pocket. One of these enzymes, Trypanosoma brucei PDE B1 (TbrPDEB1), considered drug target for treatment African sleeping sickness. Here, we elucidate molecular determinants inhibitor binding and reveal P-pocket amenable directed design. By iterative cycles design, synthesis, pharmacological evaluation by elucidating structures...
Abstract Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness ( Trypanosoma brucei rhodesiense ), nagana Chagas disease cruzi leishmaniasis Leishmania infantum ). the compounds demonstrated significant antiprotozoal activity. Specifically, 2c , 2d 4i displayed submicromolar activity T. b. with half‐maximal effective concentration (EC 50...
Polyisoprenylated benzophenones have been isolated from plants, particularly in the Clusiaceae family, and their biological properties recently received considerable attention a pharmacological point of view. The aim study was to investigate polyisoprenylated benzophenones, nemorosone guttiferone A, for antimicrobial effect against panel bacteria, fungi protozoan parasites. They showed moderate activity Gram-positive bacterium Staphylococcus aureus, while no demonstrated Escherichia coli...
Malaria, leishmaniasis and human African trypanosomiasis continue to be major public health problems in need of new more effective drugs. The aim this study was evaluate vitro antiprotozoal activity twenty endemic medicinal plants collected from the island Soqotra Indian Ocean. plant materials were extracted with methanol tested for antiplasmodial against erythrocytic schizonts Plasmodium falciparum, antileishmanial intracellular amastigotes Leishmania infantum antitrypanosomal Trypanosoma...
Metronidazole (2-methyl-5-nitro-1
The synthesis of an extensive series new squaramides with high potential in treating drug-resistant tuberculosis employing the Liebeskind-Srogl cross-coupling reaction is presented. Using protocol given and various substrates, we assessed scope limitations our methodology prepared range desired compounds. Moreover,
Drug delivery systems present an opportunity to potentiate the therapeutic effect of antileishmanial drugs. Colloidal carriers are rapidly cleared by phagocytic cells reticuloendothelial system (RES), rendering them ideal vehicles for passive targeting antileishmanials. This paper describes development poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) saponin β-aescin. NPs were prepared using combined emulsification solvent evaporation/salting-out technique. Confocal microscopy was...
Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these are limited, which invariably leads to fatal cases. Hence, there is an urgent need new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre-functionalized structures, giving rise structurally set analogs. We report on 57 with selective activity...
Inhibition of enzymes involved in the nonmevalonate pathway isoprenoid biosynthesis represents a promising strategy for development novel antimalarial agents. A small series reverse hydroxamate-based fosmidomycin analogues was synthesized and evaluated their inhibitory activity against recombinant 1-deoxy-D-xylulose 5-phosphate reductoisomerases (DXRs) Escherichia coli Plasmodium falciparum, as well vitro antiplasmodial cytotoxicity. Detailed facts importance to specialist readers are...
Human African Trypanosomiasis (HAT), caused by Trypanosoma brucei, is one of the neglected tropical diseases with a continuing need for new medication. We here describe discovery 5-phenylpyrazolopyrimidinone analogs as novel series phenotypic antitrypanosomal agents. The most potent compound, 30 (NPD-2975), has an in vitro IC50 70 nM against T. b. brucei no apparent toxicity human MRC-5 lung fibroblasts. Showing good physicochemical properties, low potential, acceptable metabolic stability,...
N-Pyrazolylcarboxamides and N-pyrazolylureas represent promising lead compounds for the development of novel antileishmanial drugs. Herein, we report late-stage diversification 3-bromopyrazoles 10 A/B 14 A by Pd-catalyzed Sonogashira Suzuki-Miyaura cross coupling reactions. The electron-withdrawing properties cyano moiety in 4-position pyrazole ring limited acylation primary amino 5-position. large set pyrazoles bearing diverse aryl alkynyl substituents 3-position was prepared...