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Artemisinin Derivatives (artemisinin + derivative)

Distribution by Scientific Domains
Chemistry83%

Selected Abstracts

Artemisinin Derivatives with Antimalarial Activity against Plasmodium falciparum Designed with the Aid of Quantum Chemical and Partial Least Squares Methods

MOLECULAR INFORMATICS, Issue 8 2003

Abstract Artemisinin derivatives with antimalarial activity against Plasmodium falciparum resistant to mefloquine are designed with the aid of Quantum Chemical and Partial Least Squares Methods. The PLS model with three principal components explaining 89.55% of total variance, Q2=0.83 and R2=0.92 was obtained for 14/5 molecules in the training/external validation set. The most important descriptors for the design of the model were one level above the lowest unoccupied molecular orbital energy (LUMO+1), atomic charges in atoms C9 and C11 (Q9) and (Q11) respectively, the maximum number of hydrogen atoms that might make contact with heme (NH) and RDF030,m (a radial distribution function centered at 3.0,Å interatomic distance and weighted by atomic masses). From a set of ten proposed artemisinin derivatives, a new compound (26), was predicted with antimalarial activity higher than the compounds reported in literature. Molecular graphics and modeling supported the PLS results and revealed heme-ligand and protein-ligand stereoelectronic relationships as important for antimalarial activity. The most active 26 and 29 in the prediction set possess substituents at C9 able to extend to hemoglobin exterior, what determines the high activity of these compounds. [source]

Growth Inhibition Activity of Thioacetal Artemisinin Derivatives Against Human Umbilical Vein Endothelial Cells.

CHEMINFORM, Issue 8 2004
Sangtae Oh
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Artemisinin Derivatives with Antimalarial Activity against Plasmodium falciparum Designed with the Aid of Quantum Chemical and Partial Least Squares Methods

MOLECULAR INFORMATICS, Issue 8 2003

Abstract Artemisinin derivatives with antimalarial activity against Plasmodium falciparum resistant to mefloquine are designed with the aid of Quantum Chemical and Partial Least Squares Methods. The PLS model with three principal components explaining 89.55% of total variance, Q2=0.83 and R2=0.92 was obtained for 14/5 molecules in the training/external validation set. The most important descriptors for the design of the model were one level above the lowest unoccupied molecular orbital energy (LUMO+1), atomic charges in atoms C9 and C11 (Q9) and (Q11) respectively, the maximum number of hydrogen atoms that might make contact with heme (NH) and RDF030,m (a radial distribution function centered at 3.0,Å interatomic distance and weighted by atomic masses). From a set of ten proposed artemisinin derivatives, a new compound (26), was predicted with antimalarial activity higher than the compounds reported in literature. Molecular graphics and modeling supported the PLS results and revealed heme-ligand and protein-ligand stereoelectronic relationships as important for antimalarial activity. The most active 26 and 29 in the prediction set possess substituents at C9 able to extend to hemoglobin exterior, what determines the high activity of these compounds. [source]

Role of medicines in malaria control and elimination

DRUG DEVELOPMENT RESEARCH, Issue 1 2010
Marian Warsame
Abstract Antimalarial medicines constitute important tools to cure and prevent malaria infections, thereby averting death and disability; their role in reducing the transmission of malaria is becoming increasingly important. Effective medicines that are currently available include artemisinin-based combination therapies (ACTs) for uncomplicated malaria, parenteral and rectal formulations of artemisinin derivatives and quinine injectables for severe malaria, and primaquine as an anti-relapse agent. These medicines are not optimal, however, owing to safety considerations in specific risk groups, complex regimens, and less than optimal formulations. The efficacy of antimalarial medicines including currently used ACTs is threatened by parasite resistance. Resistance to artemisinins has recently been identified at the Cambodia,Thailand border. Intermittent preventive treatment is constrained by the lack of a replacement for sulfadoxine-pyrimethamine. Despite increasing financial support to procure medicines, access to medicines by populations at risk of malaria, particularly in African countries, remains poor. This is largely due to weak health systems that are unable to deliver quality diagnostics and medicines through an efficient supply chain system, close at hand to the sick patient, especially in remote rural areas. Health systems are also challenged by incorrect prescribing practices in the informal and often unregulated private sector (an important provider of medicines for malaria) and the proliferation of counterfeit and substandard medicines. The provision of a more equitable access to life-saving medicines requires no less than a steady drug development pipeline for new medicines tailored to meet the challenging conditions in endemic countries, ideally single dose, highly effective against both disease and relapse-causing parasites and infective forms, extremely safe and with a long shelf life, and made available at affordable prices. Drug Dev Res 71: 4,11, 2010. © 2010 Wiley-Liss, Inc. [source]

Synthesis of "Trioxaquantel"® Derivatives as Potential New Antischistosomal Drugs

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2008
Sophie A.-L.
Abstract Over the past 20 years, praziquantel, a pyrazinoisoquinoline derivative, has become the mainstay for morbidity control of human and animal schistosomiasis. From early in their lives in vertebrate hosts, schistosomes ingest hemoglobin and aggregate the released heme as a dark pigment very similar to the hemozoin produced by Plasmodium in malaria infection. The antimalarial artemisinin derivatives have real, though low, schistosomicide activity. Because of the complementarity of the two drug classes , praziquantel and artemisinin derivatives , we designed new molecules, named trioxaquantels®, that combine the 1,2,4-trioxane unit responsible for the activity of artemisinin, and the pyrazinoisoquinoline moiety of praziquantel within a single drug. The synthesis of these new drugs and their preliminary evaluation in mice infected with Schistosoma mansoni is reported here.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

Artemisinin Derivatives with Antimalarial Activity against Plasmodium falciparum Designed with the Aid of Quantum Chemical and Partial Least Squares Methods

MOLECULAR INFORMATICS, Issue 8 2003

Abstract Artemisinin derivatives with antimalarial activity against Plasmodium falciparum resistant to mefloquine are designed with the aid of Quantum Chemical and Partial Least Squares Methods. The PLS model with three principal components explaining 89.55% of total variance, Q2=0.83 and R2=0.92 was obtained for 14/5 molecules in the training/external validation set. The most important descriptors for the design of the model were one level above the lowest unoccupied molecular orbital energy (LUMO+1), atomic charges in atoms C9 and C11 (Q9) and (Q11) respectively, the maximum number of hydrogen atoms that might make contact with heme (NH) and RDF030,m (a radial distribution function centered at 3.0,Å interatomic distance and weighted by atomic masses). From a set of ten proposed artemisinin derivatives, a new compound (26), was predicted with antimalarial activity higher than the compounds reported in literature. Molecular graphics and modeling supported the PLS results and revealed heme-ligand and protein-ligand stereoelectronic relationships as important for antimalarial activity. The most active 26 and 29 in the prediction set possess substituents at C9 able to extend to hemoglobin exterior, what determines the high activity of these compounds. [source]