RESUMO
Investigation of the freeze-dried dichloromethane: isopropanol extract of the sponge Axinella carteri Dendy, 1889 (Demospongiae: Halichondrida: Axinellidae), collected from Derawan Island, Indonesia, has led to the isolation of a new A-nor sterol with rare D-ring unsaturation, 3beta-(hydroxymethyl)-A-nor-5alpha-cholest-14-en-16-one (1). While the efficacy of the new compound is unknown, moderate cytotoxicity was observed in the fraction from which it was purified. A more polar portion of the extract afforded the known alkaloid dibromoisophakellin (2), previously isolated from an Axinella sp. The purification of the compounds was achieved on silica gel and Sephadex LH-20 supports and the identity of the compounds was established with the aid of 1D and 2D NMR spectroscopic experiments.
Assuntos
Axinella/química , Colestenonas/química , Colestenonas/isolamento & purificação , Esteróis/química , Esteróis/isolamento & purificação , Animais , Indonésia , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
A collection of an undescribed marine sponge of the genus Plakortis yielded four new "polyketide-derived" metabolites, lehualides A-D (1-4). The structures of compounds 1-4 were elucidated by interpretation of spectral data. Compound 2 demonstrated cytotoxicity against an ovarian cancer cell line, while compound 4 was active against both ovarian cancer and leukemia cell lines.
Assuntos
Antineoplásicos/isolamento & purificação , Plakortis/química , Pironas/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Havaí , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pironas/química , Pironas/farmacologiaRESUMO
The bioassay-guided fractionation of the cytotoxic crude gum obtained from the Caribbean sponge Monanchora unguifera led to the isolation and characterization of the new compounds batzelladine J (1) and crambescidic acid (2) in addition to known guanidine alkaloids ptilomycalin A (3a), ptilocaulin (4), and isoptilocaulin (5). The structures of the compounds were elucidated by interpretation of the 1D and 2D NMR experiments. The chemotaxonomic implications of these findings are discussed.
Assuntos
Antineoplásicos/isolamento & purificação , Guanidinas/isolamento & purificação , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Guanidinas/química , Guanidinas/farmacologia , Concentração Inibidora 50 , Leucemia P388 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Panamá , Células Tumorais CultivadasRESUMO
A new metabolite, poipuol (1), was isolated from an undescribed marine sponge Hyrtios sp. collected in Kauai Island, Hawaii. The structure was determined from spectroscopic data.
Assuntos
Hidrocarbonetos Clorados/isolamento & purificação , Poríferos/química , Animais , Havaí , Hidrocarbonetos Clorados/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Poríferos/metabolismoRESUMO
A cytotoxic depsipeptide, kulokekahilide-2 (1), was isolated from a cephalaspidean mollusk, Philinopsis speciosa. The structure elucidation of kulokekahilide-2 was carried out by spectroscopic analysis and chemical degradation. Kulokekahilide-2 showed potent cytotoxicity against several cell lines (P388, SK-OV-3, MDA-MB-435, and A-10 with IC50 values ranging from 4.2 to 59.1 nM) indicating cancer cell selectivity.
Assuntos
Peptídeos Cíclicos/isolamento & purificação , Animais , Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Havaí , Concentração Inibidora 50 , Leucemia P388 , Camundongos , Conformação Molecular , Estrutura Molecular , Moluscos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Estereoisomerismo , Células Tumorais CultivadasRESUMO
Three new kapakahines E-G (1-3) have been isolated from the marine sponge Cribrochalina olemda. Limited quantities of these compounds required not only NMR analysis but also FAB-MS/MS analysis for the structure elucidation. Kapakahine E showed cytotoxicity against P388 murine leukemia cells. [structure: see text]
Assuntos
Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388 , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Estereoisomerismo , Células Tumorais CultivadasRESUMO
Hectochlorin (1) was isolated from marine isolates of Lyngbya majuscula collected from Hector Bay, Jamaica, and Boca del Drago Beach, Bocas del Toro, Panama. The planar structure was deduced by one- and two-dimensional NMR spectroscopy. X-ray crystallography was used to determine the absolute stereochemistry of hectochlorin as 2S,3S,14S,22S. Hectochlorin is equipotent to jasplakinolide (5) in its ability to promote actin polymerization, but unlike jasplakinolide, is unable to displace a fluorescent phalloidin analogue from polymerized actin. In addition, hectochlorin shows both a unique profile of cytotoxicity by the COMPARE algorithm and potent inhibitory activity toward the fungus Candida albicans. Structurally, hectochlorin resembles dolabellin and the recently reported lyngbyabellin class of compounds.
Assuntos
Actinas/efeitos dos fármacos , Actinas/metabolismo , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Cianobactérias/química , Depsipeptídeos , Lactonas/isolamento & purificação , Tiazóis/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Cristalografia por Raios X , Fluoresceína-5-Isotiocianato , Concentração Inibidora 50 , Jamaica , Lactonas/química , Lactonas/farmacologia , Toxinas de Lyngbya/química , Toxinas de Lyngbya/isolamento & purificação , Toxinas de Lyngbya/farmacologia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Panamá , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Tiazóis/química , Tiazóis/farmacologiaRESUMO
Malevamide D (1), a highly cytotoxic peptide ester, and the known compound curacin D (5) were isolated from a Hawaiian sample of Symploca hydnoides. The structure of 1 was elucidated by spectroscopic analysis including NMR and high-resolution MS/MS. Partial stereochemical assignments of 1 were made by chiral HPLC analysis of acid and base hydrolysates. Malevamide D (1) demonstrated toxicity against P-388, A-549, HT-29, and MEL-28 cell lines in the subnanomolar range, while curacin D (5) was weakly cytotoxic. Malevamide D (1) is closely related to isodolastatin H (2), which was previously isolated in low yield from the sea hare Dolabella auricularia. A second Hawaiian sample of S. hydnoides yielded curacin D (5) along with the known dolastatin-10 analogue symplostatin-1 (3).
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cianobactérias/química , Depsipeptídeos , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Havaí , Hidrólise , Concentração Inibidora 50 , Leucemia P388 , Neoplasias Pulmonares , Melanoma , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oligopeptídeos/farmacologia , Estereoisomerismo , Tiazóis/química , Tiazóis/isolamento & purificação , Tiazóis/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The cytotoxic depsipeptide kulokekahilide-1, which contains two unusual amino acids, 4-phenylvaline and 3-amino-2-methylhexanoic acid, was isolated from the cephalaspidean mollusk Philinopsis speciosa. Structure elucidation of kulokekahilide-1 was carried out by spectroscopic analysis and chemical degradation. The absolute stereochemistry was determined by Marfey analysis for amino acids and chiral HPLC analysis for hydroxy acids. All four stereoisomers of 4-phenylvaline and 3-amino-2-methylhexanoic acid, which were necessary for Marfey analysis, were synthesized by use of the Heck reaction and Evans's method, respectively. Kulokekahilide-1 showed cytotoxicity against P388 murine leukemia cells with an IC(50) value of 2.1 microg/mL.
Assuntos
Antineoplásicos/isolamento & purificação , Depsipeptídeos , Moluscos/química , Peptídeos Cíclicos/isolamento & purificação , Sequência de Aminoácidos , Aminocaproatos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Caproatos/síntese química , Caproatos/química , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Havaí , Concentração Inibidora 50 , Leucemia P388 , Camundongos , Camundongos Endogâmicos , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Estereoisomerismo , Valina/análogos & derivados , Valina/síntese químicaRESUMO
The lipophilic partition of a methanol extract of the Red Sea sponge Hyrtios erecta yielded a novel pentacyclic sesterterpene ester salmahyrtisol A (1), three new scalarane-type sesterterpenes, 3-acetyl sesterstatin 1 (3), 19-acetyl sesterstatin 3 (4), and salmahyrtisol B (5), together with the previously reported sesterterpenes hyrtiosal (2), scalarolide (6), and salmahyrtisol C (7). The structure determination was based on extensive NMR studies and high-resolution mass spectral measurements. In addition, salmahyrtisol A has a previously unknown pentacyclic carbon skeleton. The new compounds show significant cytotoxicity to murine leukemia (P-388), human lung carcinoma (A-549), and human colon carcinoma (HT-29). A biosynthetic relationship between 1 and 2 is briefly discussed.
Assuntos
Antineoplásicos/isolamento & purificação , Poríferos/química , Terpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Egito , Humanos , Oceano Índico , Concentração Inibidora 50 , Leucemia P388 , Neoplasias Pulmonares , Espectrometria de Massas , Camundongos , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-Atividade , Terpenos/química , Terpenos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Four cyclic peptides, kapakahines A-D, were isolated from the marine sponge Cribrochalina olemda. Their structures including complete stereochemistry were elucidated by spectral analysis and chemical degradation. The unique structural feature of these peptides is the lack of an amide linkage between two tryptophan residues. Instead the ring is closed by a bond from the indole nitrogen of Trp-1 to the beta-carbon of Trp-2.
RESUMO
From the sponge, Ircinia dendroides, collected in Indonesia we isolated a new cyclic hexapeptide, waiakeamide (1). Its structure, consisting of three proline residues, two methionine sulfoxides, and one thiazolylphenylalanine, was elucidated by spectral analysis and chemical degradation. Isolation and structural elucidation of waiakeamide is described.
RESUMO
In addition to the previously reported bioactive kahalalide F six new peptides are described. Six of these, including kahalalide F, are cyclic depsipeptides, ranging from a C(31) tripeptide to a C(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens. The mollusk feeds on a green alga, Bryopsis sp., which has also been shown to elaborate some of these peptides in smaller yields, in addition to an acyclic analog of F, kahalalide G. The bioassay results of antitumor, antiviral, antimalarial, and OI (activity against AIDS opportunistic infections) tests are reported.