Manzamine A, a novel antitumor alkaloid from a sponge

Sakai, Ryuichi; Higa, Tatsuo; Jefford, Charles W.; Bérnardinelli, Gerald

doi:10.1021/ja00280a055

Cited by 476 publications

(307 citation statements)

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“…These compounds include the cytotoxic tertiary alkaloids haliclonacyclamines, 1) antifungal pentacyclic alkaloid papuamine, 2) antitumor alkaloid manzamine, 3) and anti-inflammatory cyclic depsipeptides halipeptins, 4) to name a few.In our previous study on the marine sponge Haliclona (Reniera) sp., we reported the isolation and structure elucidation of eight new cerebrosides 5) and a new sphingosine 6) obtained from the MeOH extract. Cerebrosides and sphingosine derivatives have been isolated from diverse natural sources, including plants, 7) marine sources, 8) microorganisms, 9) and human.…”

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New Cerebrosides from a Marine Sponge Haliclona (Reniera) sp.

Park

Mansoor

Shinde

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Sponges of the genus Haliclona have been extensively studied and afforded around 200 compounds belonging to different chemical classes. These compounds include the cytotoxic tertiary alkaloids haliclonacyclamines, 1) antifungal pentacyclic alkaloid papuamine, 2) antitumor alkaloid manzamine, 3) and anti-inflammatory cyclic depsipeptides halipeptins, 4) to name a few.In our previous study on the marine sponge Haliclona (Reniera) sp., we reported the isolation and structure elucidation of eight new cerebrosides 5) and a new sphingosine 6) obtained from the MeOH extract. Cerebrosides and sphingosine derivatives have been isolated from diverse natural sources, including plants, 7) marine sources, 8) microorganisms, 9) and human. 10) Phytosphingosine type cerebrosides are reported to exhibit bioactivities such as the antitumor, 11) antiviral, 12) inhibition of histidine decarboxylase, 13) cytotoxicity, 14) and antifungal activity. 14) In a continuing study on the same sponge, fourteen phytosphingosine type cerebrosides (1-14) were isolated from the n-hexane layer. Nine (1-9) of them contained saturated acyl chains, while five (10-14) possessed unsaturated acyl chains. Their structures were established on the basis of NMR and MS analyses, and chemical methods. Some of the cerebrosides (1, 3, 5, 7, 11, 12) contained unusual acyl chains with S-configuration. It is interesting to isolate epimeric pairs (1 : 2, 3 : 4, 5 : 6, 7 : 8) from the same specimen. Herein, we report isolation and structural characterization of cerebrosides from a marine sponge Haliclona (Reniera) sp.The brine shrimp-active MeOH extract (LD 50 126 mg/ml) of the sponge was partitioned between CH 2 Cl 2 and H 2 O. The CH 2 Cl 2 layer was further partitioned between aqueous MeOH (LD 50 27 mg/ml) and n-hexane (LD 50 45 mg/ml). Separation of the n-hexane layer by medium pressure liquid chromatography (MPLC) on a normal-phase flash column yielded 20 fractions. Fraction 16 was found to contain sugar moieties as observed in 1 H-NMR spectra, and was subjected to repeated HPLC chromatographic separation using ODS column to yield nine cerebrosides (1-9). And the mixture of fractions 10 to 15 afforded five analogues (10-14) through HPLC separation using the same condition as for fraction 16. Their structures were defined using NMR ( 1 H, 13 C, correlation spectroscopy (COSY), heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and total correlation spectroscopy (TOCSY)) and MS analysis, optical rotation data, and chemical method.Renieroside C 1 (1) was obtained as a white, amorphous solid. Its molecular formula was assigned as C 39 1-3, 5-14), along with a known analogue (4). Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy, MS spectrometry, and chemical method. The major new features of these glucocerebrosides are C 15 and C 19 acyl chains, long (C 24 -C 28 ) acyl chains, or the S-configuration of the acyl chains. It is noteworthy that both R-and S-configurations of the acyl chains wer...

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confidence: 99%

New Cerebrosides from a Marine Sponge Haliclona (Reniera) sp.

Park

Mansoor

Shinde

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…After 5 h, the reaction mixture was filtered through glass wool. The filtrate was made alkaline with 25% NH 4 OH, and the free alkaloid was extracted with EtOAc (2 mL × 4). The EtOAc-soluble ) 20) that were kept on an artificial diet that had been treated with various concentrations of the compounds under study.…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3] The manzamine alkaloids are characterized by a complex pentacyclic diamine linked to C-1 of a -carboline moiety. Manzamines have been isolated from six different genera of marine sponges: Haliclona, 4,5 Pellina, 6 Xestospongia, 7,8 Ircinia, 9 Pachypellina, 10 and Amphimedon. 11 In this paper, we describe the isolation and structure elucidation of new manzamine derivatives obtained from the Philippine marine sponge Xestospongia ashmorica n. comb.…”

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Four New Bioactive Manzamine-Type Alkaloids from the Philippine Marine Sponge Xestospongia ashmorica

Edrada¹,

Proksch²,

Wray³

et al. 1996

J. Nat. Prod.

116

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General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Analysis of the Philippine marine sponge Xestospongia ashmorica afforded four new manzamine congeners 1-4 and four known compounds 5 and 7-9. Compound 1 is the 6-deoxy derivative of manzamine X, while 2-4 are the N-oxides of manzamine J (5), 3,4-dihydromanzamine A (6), and manzamine A (7), respectively. The structures of the new compounds were unambiguously established on the basis of NMR spectroscopic ( 1 H, 13 C, COSY, 1 H-detected direct, and long-range 13 C-1 H correlations) and mass spectrometric (EI, FAB-MS, and electrospray ionization) data. Alkaloid N-oxide structures were confirmed by conversion to the corresponding tertiary bases by reduction with Zn/HCl. This is the first report of the occurrence of bioactive manzamine N-oxides in marine sponges. Compound 7 exhibited insecticidal activity toward neonate larvae of the polyphagous pest insect Spodoptera littoralis (with an ED50 of 35 ppm) when incorporated in artificial diet and offered to larvae in a chronic feeding bioassay.Compound 7 was also active against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Cytotoxicity was studied in vitro using L1578y mouse lymphoma cells. From the alkaloids studied, the N-oxides 3 and 4 were the most active (ED50 ) 1.6 µg/mL) followed by compound 7 (ED50 ) 1.8 µg/mL).

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“…17 The IR spectrum exhibited an absorption band at 1722 cm −1 , supporting the presence of a carbonyl functionality in 3. 18 manzamine A (1), 19 8-hydroxymanzamine A (10), 20 manzamine E (6), 21 manzamine F (8), 21 ircinol A, 22 and the new manzamine analogue, 8-hydroxymanzamine B (5).…”

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Manzamine B and E and Ircinal A Related Alkaloids from an Indonesian Acanthostrongylophora Sponge and Their Activity against Infectious, Tropical Parasitic, and Alzheimer's Diseases

et al. 2006

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Four new manzamine-type alkaloids, 12,28-oxamanzamine E (2), 12,34-oxa-6-hydroxymanzamine E (3), 8-hydroxymanzamine B (5), and 12,28-oxaircinal A (11), were isolated from three collections of an Indonesian sponge of the genus Acanthostrongylophora together with 13 known manzamine alkaloids, ircinal A, ircinol A, xestomanzamine A, manzamines A, E, F, J, and Y, manadomanzamines A and B, neo-kauluamine, 8-hydroxymanzamine A, and manzamine A Noxide. The structures of the new compounds were elucidated by means of 1D and 2D NMR spectroscopic methods. Three of these compounds (2, 3, and 11) possess a unique manzaminetype aminal ring system generated through an ether linkage between carbons 12-28 or between carbons 12-34. In the case of manzamine B and related metabolites, carbons 11 and 12 of the typical manzamine structure have an epoxide group and add to our growing understanding of manzamine structure-activity relationships (SAR) and metabolism. The bioactivity and SAR for a number of previously reported manzamine-related metabolites against malaria, leishmania, tuberculosis, and HIV-1 are also presented. Manzamine Y (9) showed significant inhibitory activity of GSK3, an enzyme implicated in Alzheimer's disease pathology. The toxicity of manzamine A and neo-kauluamine was evaluated against both medaka fry and eggs.A common Indo-Pacific sponge, Acanthostrongylophora sp., has been shown to be a highly rich source of bioactive manzamine-related alkaloids. [1][2][3] This class of alkaloids has been reported previously to show a number of significant biological activities including cytotoxic, 4 insecticidal, 5 antibacterial, 6 anti-inflammatory, 7 anti-infective, 8 and antiparasitic 9 * To whom correspondence should be addressed. . mthamann@olemiss.edu. HHS Public AccessAuthor manuscript J Nat Prod. Author manuscript; available in PMC 2016 June 22. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript activities, with the greatest potential for possible clinical applications existing for the control of Plasmodium falciparum and Mycobacterium tuberculosis. 10 As part of our ongoing investigations to identify new manzamines and to define the SAR as well as utilize the natural products as synthetic starting materials, [1][2][3][11][12][13] extracts of the Indonesian sponge Acanthostrongylophora sp. were investigated. In an earlier investigation, this sample yielded two new manzamine alkaloids, named 12,28-oxamanzamine A and 12,28-oxa-8-hydroxymanzamine A, and a unique ircinol A analogue together with manzamines A and F and neo-kauluamine. 2 Manzamine A (1) exhibits potent in vitro bioactivity against chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indo-China) strains of P. falciparum. Reisolation of manzamine A for pharmacokinetic and toxicology studies as well as for preparation of analogues necessitated a major collection of Acanthostrongylophora sp., yielding four new manzamine alkaloids (2, 3, 5, and 11)together with the 13 known manzamine alkaloids, which are the subject of this re...

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Manzamine A, a novel antitumor alkaloid from a sponge

Cited by 476 publications

References 2 publications

New Cerebrosides from a Marine Sponge Haliclona (Reniera) sp.

New Cerebrosides from a Marine Sponge Haliclona (Reniera) sp.

Four New Bioactive Manzamine-Type Alkaloids from the Philippine Marine Sponge Xestospongia ashmorica

Manzamine B and E and Ircinal A Related Alkaloids from an Indonesian Acanthostrongylophora Sponge and Their Activity against Infectious, Tropical Parasitic, and Alzheimer's Diseases

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