ArticleMolecules (Basel, Switzerland)2014
Several human cyclin-dependent kinase inhibitors, structurally related to roscovitine, are new anti-malarial agents.
Article in Molecules (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 20 citations in OpenAlex.
- Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis.Journal of pharmaceutical analysis · 2024Article
- Regulation of DNA replication proteins in parasitic protozoans: possible role of CDK-like kinases.Current genetics · 2016Review
- Anti-malarial Activities of Two Soil Actinomycete Isolates from Sabah via Inhibition of Glycogen Synthase Kinase 3β.Tropical life sciences research · 2016Article
- Roscovitine in cancer and other diseases.Annals of translational medicine · 2015Review
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Authors and funding
7 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs. Among newly proposed anti-malaria targets, are the P. falciparum cyclin-dependent kinases (PfCDKs). There are involved in different stages of the protozoan growth and development but share high sequence homology with human cyclin-dependent kinases (CDKs). We previously reported the synthesis of CDKs inhibitors that are structurally-related to (R)-roscovitine, a 2,6,9-trisubstituted purine, and they showed activity against neuronal diseases and cancers. In this report, we describe the synthesis and the characterization of new CDK inhibitors, active in reducing the in vitro growth of P. falciparum (3D7 and 7G8 strains). Six compounds are more potent inhibitors than roscovitine, and three exhibited IC50 values close to 1 µM for both 3D7 and 7G8 strains. Although, such molecules do inhibit P. falciparum growth, they require further studies to improve their selectivity for PfCDKs.
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