Novel cytotoxic topoisomerase II inhibiting pyrroloiminoquinones from Fijian sponges of the genus Zyzzya

Radisky, Derek C.; Radisky, Evette S.; Barrows, Louis R.; Copp, Brent R.; Kramer, Robert A.; Ireland, Chris M.

doi:10.1021/ja00058a003

Cited by 205 publications

(275 citation statements)

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“…13,14) The structures of compounds 5-9 were elucidated by 1D and 2D NMR and confirmed by comparison of the EI-MS fragmentation patterns with the NIST library of known compounds.…”

Section: 7-dimethylguanine a New Purine From A Philippine Sponge Zmentioning

confidence: 98%

“…IR spectra were recorded on a Jasco FTIR-420 spectrophotometer, using a polyethylene IR card. NMR spectra were obtained on a Varian instrument, operating at 500 MHz for 1 H-and 125 MHz for 13 C-NMR spectra. NMR spectra were recorded in D 2 O (containing three drops of CD 3 OD) and DMSO-d 6 using the residual signal of nondeuterated solvents as an internal reference.…”

Section: 7-dimethylguanine a New Purine From A Philippine Sponge Zmentioning

confidence: 99%

See 1 more Smart Citation

3,7-Dimethylguanine, a New Purine from a Philippine Sponge Zyzzya fuliginosa.

et al. 2001

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Marine organisms have proven to be a valuable source of modified purine bases and nucleosides. A number of methylated guanine or isoguanine derivatives have been reported from marine sponges [1][2][3][4] and also from some ascidians. 5-7)In our continuing search for new bioactive marine natural products, we have isolated a new purine base from a Philippine sponge, Zyzzya fuliginosa (CARTER, 1879), together with the known metabolites makaluvamines A (2), C (3), and K (4) as well as 4-hydroxyphenylacetic acid (5), methyl ester of 4-hydroxyphenylacetic acid (6), 4-hydroxyphenethyl alcohol (7), L-phenylalanine (8) and L-tryptophan (9). In this paper, we describe the isolation and characterization of the new compound, 3,7-dimethylguanine (1). Compound 1 was isolated as an amorphous white powder. N-9) suggested that the second methyl group resided on the imidazole ring, either on N-7 or N-9. Crucial long range 1 H-13 C couplings from this methyl group to C-8 (d 145.3), C-5 (d 110.5), and C-6 (d 154.6) unambiguously located it at N-7. The latter correlation (N-7-CH 3 /C-6) was also indicative of a guanine ring. Distinction between the two possible structures, 3,7-dimethylguanine (1) and 3,7-dimethylisoguanine (10) was made by MS. The fragmentation patterns of methylated purines have been investigated. 8,9) The initial expulsion of neutral cyanamide fragments consisting of N-1, C-2, and their attached substituents is a very characteristic fragmentation of the molecular ion peak of these compounds. Since guanines contain an imino substituent and isoguanines have an oxygen substitution at the C-2 position, they can be easily distinguished by EI-MS due to a one mass-unit difference.1,3) Thus, 1 showed a diagnostic ion at m/z 137.0595 due to loss of CH 2 N 2 (m/z 42) via a retro-Diels-Alder pathway. The positive mode tandem ESI- * To whom correspondence should be addressed. A new purine 3,7-dimethylguanine (1) has been isolated from the marine sponge Zyzzya fuliginosa, along with the known metabolites, makaluvamines A, C, K (2-4), 4-hydroxyphenylacetic acid (5), methyl ester of 4-hydroxyphenylacetic acid (6), 4-hydroxyphenethyl alcohol (7), L-phenylalanine (8) and L-tryptophan (9). The structure of 3,7-dimethylguanine (1) was elucidated by analysis of 1D and 2D (one-and two-dimensional) NMR [HMQC (heteronuclear multiple quantum coherence), gHMBC (heteronuclear multiple bond connectivity), 1 H-15 N gHMBC] data, mass spectroscopy data, and by comparison with 3,7-dimethylisoguanine (10).

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“…13,14) The structures of compounds 5-9 were elucidated by 1D and 2D NMR and confirmed by comparison of the EI-MS fragmentation patterns with the NIST library of known compounds.…”

Section: 7-dimethylguanine a New Purine From A Philippine Sponge Zmentioning

confidence: 98%

Section: 7-dimethylguanine a New Purine From A Philippine Sponge Zmentioning

confidence: 99%

3,7-Dimethylguanine, a New Purine from a Philippine Sponge Zyzzya fuliginosa.

et al. 2001

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“…Using this assay, the marine invertebrate pyrroloiminoquinones shown in Fig. (7), makaluvamines (from the sponge Zyzzya fuliginosa) [150,151] and wakayin (from the ascidian Clavelina sp.) [152] were isolated.…”

Section: Topoisomerasesmentioning

confidence: 99%

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

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Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.

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“…Moreover, this structural moiety has also been explored as an useful synthon for the synthesis of structurally diverse complex heterocycles such as benzo-[a]-quinazolidine-2-ones, 8 hexahydropyrido-[3,4-c]-[1,5]-benzothiazepines, 9 5-(diethoxyphosphoryl)-1-aryl-2-alkyl/aryl-2,3-dihydro-4-pyridones, 10 3-aminopiperidines, 11 methyl indolo-[2,3-a]quinazolidin-2-acetate, 12 and synthesis of various alkaloids such as guettardine, 15-epiguettardine, 13 E-azaburnamine, 14 makaluvamine A & C, 15 veiutamine, 16 and synthesis of the fundamental tetracyclic skeleton of ervitsine and 20-de-ethylidine-6,16-dihydro analogues. 17 In view of their importance and wide applications, their synthesis has gained considerable attention, and therefore, become a focus of synthetic organic chemistry.…”

Section: Introductionmentioning

confidence: 99%

An efficient method for the synthesis of substituted N-aryl lactams

Chaturvedi¹,

Chaturvedi²,

Dash³

et al. 2015

10.5267/j.ccl

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A quick, efficient, and one-pot method for the synthesis of substituted N-aryl lactams through the reaction of various kinds of corresponding substituted arenes with a variety of ω-azido alkanoic acids using trifluoromethanesulfonic acid (triflic acid) at room temperature, by insitu involvement of Friedel-Crafts reaction followed by intramolecular Schmidt rearrangement was developed, and afforded good to excellent yields.

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Novel cytotoxic topoisomerase II inhibiting pyrroloiminoquinones from Fijian sponges of the genus Zyzzya

Cited by 205 publications

References 3 publications

3,7-Dimethylguanine, a New Purine from a Philippine Sponge Zyzzya fuliginosa.

3,7-Dimethylguanine, a New Purine from a Philippine Sponge Zyzzya fuliginosa.

Mechanism Targeted Discovery of Antitumor Marine Natural Products

An efficient method for the synthesis of substituted N-aryl lactams

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