New Manzamine Alkaloids with Potent Activity against Infectious Diseases

Sayed, Khalid A. El; Kelly, Michelle; Kara, U. A. K.; Ang, Kenny Kean‐Hooi; Katsuyama, Iwao; Dunbar, D. Chuck; Khan, and A. A.; Hamann, Mark T.

doi:10.1021/ja002073o

Cited by 126 publications

(123 citation statements)

References 17 publications

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“…Several Indonesian sponges have been identified as a rich source of manzamine alkaloids. The yield of ent-8-hydroxymanzamine F (34) was shown to be 1.24% (22), and the yield of manzamine A from the same sponge can reach as much as 5%. (+)-Aeroplysinin-1 (36) was first isolated from Aplysina aerophoba (23).…”

Section: Marine-derived Compoundsmentioning

confidence: 99%

Marine Natural Products as Prototype Agrochemical Agents

Peng

Shen²,

Ka³

et al. 2003

J. Agric. Food Chem.

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In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents.

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Section: Marine-derived Compoundsmentioning

confidence: 99%

Marine Natural Products as Prototype Agrochemical Agents

Peng

Shen²,

Ka³

et al. 2003

J. Agric. Food Chem.

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“…1 These compounds exhibit a diverse range of bioactivities including cytotoxicity, 1 insecticidal, 2 and antibacterial 3 as well as the exciting curative activity against malaria in animal models. 4,5 Since the first report of manzamine A, an additional 40 manzamine-type alkaloids have been reported from nine different sponge genera. 6,7 In our continuing search for manzamine-related alkaloids with significant activity against infectious diseases, we have identified several novel manzamine alkaloids from an Indonesian sponge, and herein we describe their structure determination and biological activity.…”

mentioning

confidence: 99%

New Manzamine Alkaloids with Activity against Infectious and Tropical Parasitic Diseases from an Indonesian Sponge

et al. 2003

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Eleven manzamine type alkaloids, two β-carbolines, and five nucleosides have been isolated from an Indonesian sponge. Among these are the previously characterized 12,34-oxamanzamine A, 12,34-oxamanzamine E, manzamine A (1), 8-hydroxymanzamine A, 6-deoxymanzamine X, manzamine E (2), manzamine X, manzamine F (4), norharman, thymine, 2′,3′-didehydro-2′,3′-dideoxyuridine, uracil, thymidine, and 2′-deoxyuridine. The structures for the five new compounds have been assigned as 32,33-dihydro-31-hydroxymanzamine A (3), 32,33-dihydro-6-hydroxymanzamine A-35-one (5), des-N-methylxestomanzamine A (6), 32,33-dihydro-6,31-dihydroxymanzamine A (7), and 1,2,3,4-tetrahydronorharman-1-one (8), on the basis of NMR and X-ray data. The bioactivity and SAR of the manzamines against malaria, TB, and leishmania are also presented. The structural revision of two previously reported pyrazoles as uracil and thymine is also discussed.Manzamines are unique β-carboline alkaloids isolated from Indo-Pacific sponges and characterized by having an intricate nitrogen-containing polycyclic system. In 1986, Higa and co-workers first reported manzamine A from the Okinawan sponge of the genus Haliclona. 1 These compounds exhibit a diverse range of bioactivities including cytotoxicity, 1 insecticidal, 2 and antibacterial 3 as well as the exciting curative activity against malaria in animal models. 4,5 Since the first report of manzamine A, an additional 40 manzamine-type alkaloids have been reported from nine different sponge genera. 6,7 In our continuing search for manzamine-related alkaloids with significant activity against infectious diseases, we have identified several novel manzamine alkaloids from an Indonesian sponge, and herein we describe their structure determination and biological activity. *To whom correspondence should be addressed. Tel: (662) 915-5730. Fax: (662) 915-6975. mthamann@olemiss.edu. Supporting Information Available: Copies of 1 H and 13 C NMR spectra for all new compounds, HMQC spectra for 3, 5-7, HMBC spectra for 5-8, and X-ray data for 3. This material is available free of charge via the Internet at http://pubs.acs.org. (Table 1) includes aromatic proton resonances similar to those of manzamine E. 12 Spectral data of how 3 differs from manzamine E (2) includes the presence of 13 CH carbons (manzamine E has 12 CH carbons) and the absence of the low-field C-31 carbonyl carbon signal of manzamine E. In place of the carbonyl carbon compound 3 has a signal at 70.9 ppm, which correlates with a multiplet at 4.05 ppm in the HMQC spectrum. The presence of this new OH-functionality is confirmed by a number of long-range 1 H-13 C correlations H 2 -29 and H 2 -33 to C-31, Figure 1 HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript C-12, C-24, C-25, C-26, and C-34 of 3 were elucidated to be the same as those of manzamine E by NOESY data as well as comparable 13 C chemical shifts. In addition both compounds were isolated from the same sponge and possessed dextrorotation. The relative config...

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“…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.…”

Section: Author Manuscript Author Manuscriptmentioning

confidence: 99%

“…[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 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.…”

mentioning

confidence: 99%

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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New Manzamine Alkaloids with Potent Activity against Infectious Diseases

Cited by 126 publications

References 17 publications

Marine Natural Products as Prototype Agrochemical Agents

Marine Natural Products as Prototype Agrochemical Agents

New Manzamine Alkaloids with Activity against Infectious and Tropical Parasitic Diseases from an Indonesian Sponge

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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