8-Hydroxymanzamine A, a β-Carboline Alkaloid from a Sponge, Pachypellina sp.

Ichiba, Toshio; Corgiat, Jay M.; Scheuer, Paul J.; Kelly‐Borges, Michelle

doi:10.1021/np50103a027

Cited by 96 publications

(71 citation statements)

References 2 publications

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“…5) was first isolated in 1986 from a sponge of genus Haliclona [85], (+)-8-hydroxymanzamine A (78) from the Pachypellina sp. [86] and manzamine A N-oxide (79) from the marine sponge Xestospongia ashmorica [87] resulted active against P. falciparum. Due to their relevant role, it was important to find suitable methods for biological testing and applications.…”

Section: Alkaloidsmentioning

confidence: 99%

Synthesis of Marine Natural Products with Antimalarial Activity

Mancini¹,

Guella²,

Defant

2008

MRMC

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Section: Alkaloidsmentioning

confidence: 99%

Synthesis of Marine Natural Products with Antimalarial Activity

Mancini¹,

Guella²,

Defant

2008

MRMC

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“…In our ongoing research for neuronal differentiation inducers from marine invertebrates, 8) we isolated two manzamine-class alkaloids manzamine A (1) and 8-hydroxymanzamine A (2) 9) as free base forms, together with three known manzamine alkaloids manzamine E (3), 10) manzamine F (4), 10) and manzamine X (5) 11) from an Okinawan marine sponge Acanthostrongylophora aff. ingens.…”

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confidence: 99%

Neuritogenic Activity-Guided Isolation of a Free Base Form Manzamine A from a Marine Sponge, Acanthostrongylophora aff. ingens (Thiele, 1899)

Zhang

Higuchi

Miyamoto

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Manzamines have been reported to show a number of significant biological activities including insecticidal, 1) cytotoxicity, 2) antibacterial, 3) anti-HIV-I, 4) anti-infective, 5) antiAlzheimer diseases, 6) and anti-malarial activity. 7) Manzamine A · HCl (6) was first isolated from the marine sponge Haliclona sp. as an antitumor alkaloid by Higa's group.2) Histrorically, manzamine A was also isolated from a marine sponge, Pellina sp. as an antimicrobial alkaloid, and named keramamine-A by Nakamura's group.3) Manzamine A and keramamine-A were also isolated as a hydrochloric salt, and these structures were determined by X-ray analysis. In our ongoing research for neuronal differentiation inducers from marine invertebrates, 8) we isolated two manzamine-class alkaloids manzamine A (1) and 8-hydroxymanzamine A (2) 9) as free base forms, together with three known manzamine alkaloids manzamine E (3), 10) manzamine F (4), 10) and manzamine X (5) 11) from an Okinawan marine sponge Acanthostrongylophora aff. ingens.1 H-and 13 C-NMR spectra of 1 and 2 were quite different from the reported data. We investigated their structure determination by using 2D-NMR extensively. This paper reports the isolation, structural elucidation and neuritogenic activity against mouse neurobrastoma cell lines (Neuro 2a) of these manzamine-class alkaloids.The Et 2 O soluble fraction obtained from the EtOH extract of a Japanese marine sponge, A. ingens collected at Hedo Peninsula, Okinawa showed neuritogenic activity against Neuro 2a. Bioassay guided separation of the active fraction by Sephadex LH-20 and silica gel chromatography to give two active alkaloids manzamine A (1) and 8-hydroxymanzamine A (2) together with three known alkaloids manzamine E (3), manzamine F (4), and manzamine X (5) (Chart 1).Manzamine A (1) was obtained as a yellow solid, positive to Dragendorff reagent. The EI-MS showed a molecular ion peak at m/z 548, and the molecular formula was determined as C 36 H 44 N 4 O [MϩH] ϩ from the HR-ESI-MS. The UV spectral showed characteristic absorbance of the b-carboline chromophore at 219, 237, 279, 347, and 357 nm. On the basis of 1D-NMR and COSY, TOCSY, HSQC, HMBC, and HSQC-TOCSY spectral data, 1 consists of a b-carboline substituent, two six-membered rings, a 13-membered macrocycle consisting of a chain of nine carbon atoms bridging two six-membered rings, and an eight-numbered ring. It has been suggested that 1 has the same planar structure as manzamine A · HCl (6) (Fig. 1). The comparison of 1 H-and 13 C-NMR chemical shifts between 1 and 6, and the large differences at C26-C29 and C32-C34 in eight-numbered rings were ob- Two manzamine-class alkaloids, manzamine A (1) and 8-hydroxymanzamine (2) were isolated from a Japanese marine sponge Acanthostrongylophora aff. ingens, together with three known alkaloids manzamine E (3), manzamine F (4), and manzamine X (5). The spectral features of 1 and 2 were different from the reported data. Detailed structure analysis using 2D NMR revealed the structure of 1 and 2 as a free base form ...

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“…The origin, isolation, and chemistry of various manzamines have been reviewed (6,13), with the complete synthesis of manzamine A being recently reported (20). The manzamines previously received considerable interest because of their potential as anticancer agents, with both manzamine A and manzamine F inhibiting the growth of P-388 mouse leukemia cells (6) and 8-hydroxymanzamine A showing moderate cytotoxicity against KB and LoVo cells (7). We have now found that manzamine A and 8-hydroxymanzamine A significantly inhibit malaria parasites not only in vitro but also in vivo.…”

mentioning

confidence: 99%

In Vivo Antimalarial Activity of the Beta-Carboline Alkaloid Manzamine A

Ang

Holmes

Higa

et al. 2000

Antimicrob Agents Chemother

213

136

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Manzamine A, a ␤-carboline alkaloid present in several marine sponge species, inhibits the growth of the rodent malaria parasite Plasmodium berghei in vivo. More than 90% of the asexual erythrocytic stages of P. berghei were inhibited after a single intraperitoneal injection of manzamine A into infected mice. A remarkable aspect of manzamine A treatment is its ability to prolong the survival of highly parasitemic mice, with 40% recovery 60 days after a single injection. Oral administration of an oil suspension of manzamine A also produced significant reductions in parasitemia. The plasma manzamine A concentration peaked 4 h after injection and remained high even at 48 h. Morphological changes of P. berghei were observed 1 h after treatment of infected mice. (؊)-8-Hydroxymanzamine A also displayed antimalarial activity, whereas manzamine F, a ketone analog of manzamine A, did not. Our results suggest that manzamine A and (؊)-8-hydroxymanzamine A are promising new antimalarial agents.Malaria remains the most devastating infectious parasitic disease, inflicting both death and economic losses on at least half the world's population. Numerous attempts have been made to control the disease by using vector control measures and/or chemoprophylaxis, but they have had limited success (18). Immunoprophylaxis holds promise, but effective vaccines are still not available. Presently, the most effective way of dealing with malaria is the administration of chemotherapeutic agents. Although drug treatments of malaria are currently the best means of disease management, there is an urgent need for the development of structurally novel and effective antimalarial drugs because of increasing resistance to most presently available antimalarial drugs (15,16,19).Some of the most effective antimalarial drugs available, quinine and artemisinin, are natural products derived from terrestrial plants. However, recent research suggests that marine organisms may also produce compounds with activity against malaria parasites (4,11,21). Manzamines are a structurally unique group of ␤-carboline alkaloids isolated from several marine sponge species found in waters of the Indian Ocean and the Pacific Ocean. Manzamine A (Fig. 1) was initially isolated from a Haliclona sp. (17) but has been subsequently found in other genera of marine sponges, including Pellina (14), Pachypellina (7), Xestospongia (3, 8), Ircinia (10), and Amphimedon (9). In addition, more than 30 other compounds structurally related to manzamine A have been isolated from sponges and characterized; these include 8-hydroxymanzamine A and the ketone derivative manzamine F (Fig. 1). The origin, isolation, and chemistry of various manzamines have been reviewed (6, 13), with the complete synthesis of manzamine A being recently reported (20). The manzamines previously received considerable interest because of their potential as anticancer agents, with both manzamine A and manzamine F inhibiting the growth of P-388 mouse leukemia cells (6) and 8-hydroxymanzamine A showing moderate cytotoxici...

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8-Hydroxymanzamine A, a β-Carboline Alkaloid from a Sponge, Pachypellina sp.

Abstract: The previously described manzamine A [1] and the new 8-hydroxymanzamine A [2] were isolated from an undescribed sponge, Pachypellina sp. Both compounds exhibit moderate antitumor and anti-HSV-II activity.

Cited by 96 publications

References 2 publications

Synthesis of Marine Natural Products with Antimalarial Activity

Synthesis of Marine Natural Products with Antimalarial Activity

Neuritogenic Activity-Guided Isolation of a Free Base Form Manzamine A from a Marine Sponge, Acanthostrongylophora aff. ingens (Thiele, 1899)

In Vivo Antimalarial Activity of the Beta-Carboline Alkaloid Manzamine A

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