title: Antimalarial Isocyano and Isothiocyanato Sesquiterpenes with Tri- and Bicyclic Skeletons from the Nudibranch Phyllidia ocellata.
abstract: Five new isocyano/isothiocyanato sesquiterpenes (1-5) with tri- or bicyclic carbon skeletons have been characterized from Australian specimens of the nudibranch Phyllidia ocellata. Spectroscopic analyses at 900 MHz were informed by DFT calculations. The 1S, 5S, 8R configuration of 2-isocyanoclovene (1) was determined by X-ray crystallographic analysis of formamide 6. A biosynthetic pathway to clovanes 1 and 2 from epicaryolane precursors is proposed. Isocyanides 1, 2, and 4 showed activity against Plasmodium falciparum (IC50 0.26-0.30 μM), while isothiocyanate 3 and formamide 6 had IC50 values of >10 μM.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: White
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Pierens
authors.affiliation: §Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Skinner-Adams
authors.affiliation: §Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Andrews
authors.forename: Paul V
authors.initials: PV
authors.lastname: Bernhardt
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Krenske
authors.affiliation: ⊥Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Pozzuoli (Na), 80078, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Mollo
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Garson
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D018360:Crystallography, X-Ray; D049851:Gastropoda / Q000737:chemistry*; D017953:Isocyanates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017879:Isothiocyanates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D017953:Isocyanates; D017879:Isothiocyanates; D012717:Sesquiterpenes