The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism(379 views)(PDF public172 views) Persico M, Fattorusso R, Taglialatela-scafati O, Chianese G, De Paola I, Zaccaro L, Rondinelli F, Lombardo M, Quintavalla A, Trombini C, Fattorusso E, Fattorusso C, Farina B
University of Naples "Federico II", Department of Pharmacy, Via D. Montesano 49, Napoli, 80131, Italy., Italian Malaria Network - Centro Interuniversitario di Ricerca Sulla Malaria (CIRM) Department of Experimental Medicine and Biochemical Science, Via Del Giochetto, Perugia, Italy., Second University of Naples, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Via Vivaldi 43, Caserta, 81100, Italy., Institute of Biostructures and Bioimages (IBB) CNR, Via Mezzocannone 16, Naples, 80134, Italy., Alma Mater Studiorum University of Bologna, Department of Chemistry "G. Ciamician", Via Selmi 2, Bologna, 40126, Italy., Advanced Accelerator Applications, Via Vivaldi 43, Caserta, 81100, Italy.,
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The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism
In the present work we performed a combined experimental and computational study on the interaction of the natural antimalarial endoperoxide plakortin and its synthetic analogue 4a with heme. Obtained results indicate that the studied compounds produce reactive carbon radical species after being reductively activated by heme. In particular, similarly to artemisinin, the formation of radicals prone to inter-molecular reactions should represent the key event responsible for Plasmodium death. To our knowledge this is the first experimental investigation on the reductive activation of simple antimalarial endoperoxides (1,2-dioxanes) by heme and results were compared to the ones previously obtained from the reaction with FeCl2. The obtained experimental data and the calculated molecular interaction models represent crucial tools for the rational optimization of our promising class of low-cost synthetic antimalarial endoperoxides.
The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(596 views) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 ViewExport to BibTeXExport to EndNote