title: 4-Acetoxydolastane diterpene from the Brazilian brown alga Canistrocarpus cervicornis as antileishmanial agent.
abstract: Natural marine products have shown an interesting array of diverse and novel chemical structures with potent biological activities. Our study reports the antiproliferative assays of crude extracts, fraction and pure compound (4R,9S,14S)-4α-acetoxy-9β,14α-dihydroxydolast-1(15),7-diene (1) obtained from brown alga Canistrocarpus cervicornis showing the antileishmanial activity. We showed that 1 had a dose-dependent activity during 72 h of treatment, exhibiting IC(50) of 2.0 μg/mL, 12.0 μg/mL, and 4.0 μg/mL for promastigote, axenic amastigote and intracellular amastigote forms of Leishmania amazonensis, respectively. A cytotoxicity assay showed that the action of the isolated compound 1 was 93.0 times less toxic to the macrophage than to the protozoan. Additionally, compound 1 induced ultrastructural changes, including extensive mitochondrial damage; decrease in Rh123 fluorescence, suggesting interference with the mitochondrial membrane potential; and lipid peroxidation in parasite cells. The use of 1 from C. cervicornis against L. amazonensis parasites might be of great interest as a future alternative to the development of new antileishmanial drugs.
authors.affiliation: Postgraduate Program in Microbiology, State University of Londrina, Highway Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Londrina, Parana, Brazil.
authors.forename: Adriana Oliveira Dos
authors.initials: AOD
authors.lastname: Santos
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Laboratory of Technological Innovation in the Development of Drugs and Cosmetics, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Elizandra Aparecida
authors.initials: EA
authors.lastname: Britta
authors.affiliation: Postgraduate Program in Chemistry, Department of Fundamental Chemistry, Federal University of Pernambuco, CEP 50670-901, Recife, Pernambuco, Brazil.
authors.forename: Everson Miguel
authors.initials: EM
authors.lastname: Bianco
authors.affiliation: Postgraduate Program in Pharmaceutical Sciences, Laboratory of Technological Innovation in the Development of Drugs and Cosmetics, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Tania
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.affiliation: Postgraduate Program in Microbiology, State University of Londrina, Highway Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Londrina, Parana, Brazil.|Postgraduate Program in Pharmaceutical Sciences, Laboratory of Technological Innovation in the Development of Drugs and Cosmetics, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Benedito Prado Dias
authors.initials: BPD
authors.lastname: Filho
authors.affiliation: Department of Marine Biology, Federal Fluminense University, PO Box 100644, CEP 24001-970, Niteroi, Rio de Janeiro, Brazil.
authors.forename: Renato Crespo
authors.initials: RC
authors.lastname: Pereira
authors.affiliation: Postgraduate Program in Microbiology, State University of Londrina, Highway Celso Garcia Cid, PR 445, Km 380, CEP 86051-990, Londrina, Parana, Brazil.|Postgraduate Program in Pharmaceutical Sciences, Laboratory of Technological Innovation in the Development of Drugs and Cosmetics, State University of Maringa, Colombo Avenue 5790, CEP 87020-900, Maringa, Parana, Brazil.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
mesh_terms: D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001938:Brazil; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000459:Phaeophyceae / Q000737:chemistry*
chemical_list: C542295:4-acetoxy-9,14-dihydroxydolast-1(15),7-diene; D000981:Antiprotozoal Agents; D004224:Diterpenes