title: Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta.
abstract: Bastimolide A (1), a polyhydroxy macrolide with a 40-membered ring, was isolated from a new genus of the tropical marine cyanobacterium Okeania hirsuta. This novel macrolide was defined by spectroscopy and chemical reactions to possess one 1,3-diol, one 1,3,5-triol, six 1,5-diols, and one tert-butyl group; however, the relationships of these moieties to one another were obscured by a highly degenerate (1)H NMR spectrum. Its complete structure and absolute configuration were therefore unambiguously determined by X-ray diffraction analysis of the nona-p-nitrobenzoate derivative (1d). Pure bastimolide A (1) showed potent antimalarial activity against four resistant strains of Plasmodium falciparum with IC50 values between 80 and 270 nM, although with some toxicity to the control Vero cells (IC50 = 2.1 μM), and thus represents a potentially promising lead for antimalarial drug discovery. Moreover, rigorous establishment of its molecular arrangement gives fresh insight into the structures and biosynthesis of cyanobacterial polyhydroxymacrolides.
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.|‡Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, P.R. China.
authors.forename: Chang-Lun
authors.initials: CL
authors.lastname: Shao
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.|§Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.|∥Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Clayton, Apartado 0816-02852, Panama.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Linington
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.|∥Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Clayton, Apartado 0816-02852, Panama.|⊗Division of Medicinal Chemistry, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, United States.
authors.forename: Marcy J
authors.initials: MJ
authors.lastname: Balunas
authors.affiliation: ∥Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Clayton, Apartado 0816-02852, Panama.
authors.forename: Argelis
authors.initials: A
authors.lastname: Centeno
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Boudreau
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: ⊥Department of Biological Sciences, Florida International University, Miami, Florida 33199, United States.
authors.forename: Niclas
authors.initials: N
authors.lastname: Engene
authors.affiliation: ∥Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia, Clayton, Apartado 0816-02852, Panama.
authors.forename: Carmenza
authors.initials: C
authors.lastname: Spadafora
authors.affiliation: #Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, United States.
authors.forename: Tina S
authors.initials: TS
authors.lastname: Mutka
authors.affiliation: #Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, United States.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
authors.forename: Lena
authors.initials: L
authors.lastname: Gerwick
authors.affiliation: ‡Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, P.R. China.
authors.forename: Chang-Yun
authors.initials: CY
authors.lastname: Wang
authors.affiliation: †Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.|$Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000458:Cyanobacteria / Q000737:chemistry*; D004351:Drug Resistance; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D018942:Macrolides; C000603237:bastimolide A