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Drug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.
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http://dx.doi.org/10.1016/j.bmcl.2024.129894 | DOI Listing |
J Med Chem
May 2025
Holistic Drug Discovery and Development (H3D) Centre, University of Cape Town, Rondebosch 7701, South Africa.
In the search for novel chemotypes with high sp character and activity against the human malaria parasite , a spiroindoline series was identified from a phenotypic high-throughput screening campaign. The spiroindoline hit displayed good activity against both drug-sensitive and multidrug-resistant strains, making it an attractive starting point for hit-to-lead progression. Structure-activity relationship studies led to the identification of a novel pyridylspiroindoline frontrunner () with improved antiplasmodial activity, aqueous solubility, and microsomal metabolic stability.
View Article and Find Full Text PDFRSC Med Chem
April 2025
Institute of Pharmacy and Food Chemistry, Würzburg University Am Hubland 97074 Würzburg Germany.
The synthesis of pentacyclic 6,13-pyrazino[1,2-;4,5-']diindole analogues and their evaluation for antiplasmodial activity against 3D7 strains using [H]hypoxanthine incorporation and SYBR® Green assays are reported. While the unsubstituted analogues are characterized by only weak antimalarial activity, introduction of one or two basic side-chains led to substantially increased antiplasmodial activity and reduced cytotoxicity against macrophage J774.1 cells.
View Article and Find Full Text PDFChemMedChem
June 2025
Laboratoire de chimie de coordination du CNRS LCC-CNRS, Inserm ERL 1289 MAAP, Université de Toulouse, 205 route de Narbonne, 31077, Toulouse cedex, France.
This review is focused on hybrid molecules defined as chemical entities with two or more structural domains, as antimalarial drug-candidates, over the past 25 years. Due to their different pharmacophores, such hybrids can interact with a single biological target by different and complementary mechanisms; they can also act simultaneously on several targets having complementary biological functions (dual mode of action), and can theoretically reduce the selection of parasite drug-resistance. This review is not an exhaustive report of all hybrid drugs tested on malaria parasites but a selection of hybrids with pharmacologically relevant antiplasmodial properties and original chemical structures.
View Article and Find Full Text PDFJ Nat Prod
April 2025
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Evin 1983969411, Tehran, Iran.
Perovskones, intricate triterpenoids with potent antiplasmodial activity, predominantly derive from DC. ex Benth. In this study, ample quantities of the parent compound, perovskone (), were isolated from the plant.
View Article and Find Full Text PDFBioorg Med Chem
June 2025
Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland. Electronic address:
Malaria remains a significant public health issue and one of the leading causes of child mortality worldwide. Due to the growing problem of drug resistance, new modes of fighting the disease are searched for. In this context, ionophore antibiotics, natural compounds with high potential for combating parasitic diseases, deserve special attention.
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