title: Cytotoxic Plakortides from the Brazilian Marine Sponge Plakortis angulospiculatus.
abstract: Three new plakortides, 7,8-dihydroplakortide E (1), 2, and 10, along with known natural products 3, 4, spongosoritin A (5), 6-8, and plakortide P (9), were isolated from Brazilian specimens of Plakortis angulospiculatus. Compounds 2, 3, 5, and 7-9 displayed cytotoxic activities with IC50 values ranging from 0.2 to 10 μM. Compounds that contained a dihydrofuran ring were generally less active and displayed time dependence in their activity. The activities of compounds 2 and 7-9, carboxylic acids bearing a common six-membered endoperoxide, were higher overall than for compounds 3 and 5. The modes underlying the cytotoxic actions of plakortides 2, 3, 5, 7, and 9 were further investigated using HCT-116 cells. While dihydrofurans 3 and 5 induce a G0/G1 arrest, six-membered peroxides 2, 7, and 9 delivered a G2/M arrest and an accumulation of mitotic figures, indicating a distinctly different antimitotic response. Confocal analysis indicated that microtubules were not altered after treatment with 2, 7, or 9, therein suggesting that the mitotic arrest may be unrelated to cytoskeletal targets. Overall, we find that two related classes of natural products obtained from the same extract offer cytostatic activity, yet they do so through discrete pathways.
authors: †Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, 60.430-270, Brazil.
authors: Evelyne A
authors: EA
authors: Santos
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Amanda L
authors: AL
authors: Quintela
authors: §Instituto de Ciências do Mar, LABOMAR, Universidade Federal do Ceará, Fortaleza, 60.165-081, Brazil.
authors: Elthon G
authors: EG
authors: Ferreira
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Thiciana S
authors: TS
authors: Sousa
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Francisco das Chagas L
authors: Fd
authors: Pinto
authors: ⊥Departamento de Invertebrados, Museu Nacional, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, 20.940-040, Brazil.
authors: Eduardo
authors: E
authors: Hajdu
authors: Mariana S
authors: MS
authors: Carvalho
authors: ⊥Departamento de Invertebrados, Museu Nacional, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, 20.940-040, Brazil.
authors: Sula
authors: S
authors: Salani
authors: †Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, 60.430-270, Brazil.
authors: Danilo D
authors: DD
authors: Rocha
authors: †Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, 60.430-270, Brazil.
authors: Diego V
authors: DV
authors: Wilke
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Maria da Conceição M
authors: Mda C
authors: Torres
authors: §Instituto de Ciências do Mar, LABOMAR, Universidade Federal do Ceará, Fortaleza, 60.165-081, Brazil.
authors: Paula C
authors: PC
authors: Jimenez
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Edilberto R
authors: ER
authors: Silveira
authors: ∥Xenobe Research Institute, P.O. Box 3052, San Diego, California 92163-1052, United States.
authors: James J
authors: JJ
authors: La Clair
authors: ‡Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, 60.021-970, Brazil.
authors: Otília Deusdênia L
authors: OD
authors: Pessoa
authors: †Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, 60.430-270, Brazil.|§Instituto de Ciências do Mar, LABOMAR, Universidade Federal do Ceará, Fortaleza, 60.165-081, Brazil.
authors: Letícia V
authors: LV
authors: Costa-Lotufo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001938:Brazil; D004146:Dioxanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D015394:Molecular Structure; D010545:Peroxides / Q000494:pharmacology; D047229:Plakortis; D011161:Porifera
chemical_list: C000599578:7,8-dihydroplakortide E; D000970:Antineoplastic Agents; D004146:Dioxanes; D010545:Peroxides