title: Computer-Aided Drug Discovery from Marine Compounds: Identification of the Three-Dimensional Structural Features Responsible for Antimalarial Activity.
abstract: An integrated computational approach, based on molecular dynamics/mechanics, semi-empirical, and DFT calculations as well as dynamic docking studies, has been employed to gain insight into the mechanism of action of new antimalarial agents characterized by the scaffold of the marine compounds plakortin and aplidinone. The results of this approach show that these molecules, after interaction with Fe(II), likely coming from the heme molecule, give rise to the formation of radical species, that should represent the toxic intermediates responsible for subsequent reactions leading to plasmodium death. The three-dimensional structural requirements necessary for the activity of these new classes of antimalarial agents have been identified and discussed throughout the chapter.
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Via D. Montesano 49, 80131, Naples, Italy. caterina.fattorusso@unina.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fattorusso
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Persico
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rondinelli
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Orteca
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Via D. Montesano 49, 80131, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Dato
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry*; D059001:Aquatic Organisms / Q000737:chemistry*; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000639:trends; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000639:trends; D008956:Models, Chemical; D008968:Molecular Conformation; D062105:Molecular Docking Simulation / Q000639:trends*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011487:Protein Conformation; D013678:Technology, Pharmaceutical / Q000639:trends
chemical_list: D000962:Antimalarials; D001688:Biological Products; D004364:Pharmaceutical Preparations