Differential inhibition of eukaryotic DNA polymerases by halenaquinol sulfate, a <i>p</i>‐hydroquinone sulfate obtained from a marine sponge

Shioda, Masaki; Kano, Kazukaka; Kobayashi, Mariko; Kitagawa, Isao; Shoji, Mami; Yoshida, Shonen; Ikegami, Susumu

doi:10.1016/0014-5793(94)00777-2

Cited by 10 publications

(3 citation statements)

References 23 publications

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“…A recent study, by Takaku et al described 82 as a novel RAD51 inhibitor that specifically inhibits RAD51-dsDNA binding [ 121 ]. Compound 83 inhibited eukaryotic DNA polymerases to varying degrees [ 122 ].…”

Section: Tongan Marine Invertebratesmentioning

confidence: 99%

Natural Products from Tongan Marine Organisms

et al. 2021

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The islands of the South Pacific Ocean have been in the limelight for natural product biodiscovery, due to their unique and pristine tropical waters and environment. The Kingdom of Tonga is an archipelago in the central Indo-Pacific Ocean, consisting of 176 islands, 36 of which are inhabited, flourishing with a rich diversity of flora and fauna. Many unique natural products with interesting bioactivities have been reported from Indo-Pacific marine sponges and other invertebrate phyla; however, there have not been any reviews published to date specifically regarding natural products from Tongan marine organisms. This review covers both known and new/novel Marine Natural Products (MNPs) and their biological activities reported from organisms collected within Tongan territorial waters up to December 2020, and includes 109 MNPs in total, the majority from the phylum Porifera. The significant biological activity of these metabolites was dominated by cytotoxicity and, by reviewing these natural products, it is apparent that the bulk of the new and interesting biologically active compounds were from organisms collected from one particular island, emphasizing the geographic variability in the chemistry between these organisms collected at different locations.

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Section: Tongan Marine Invertebratesmentioning

confidence: 99%

Natural Products from Tongan Marine Organisms

et al. 2021

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“…(9). Halenaquinol sulfate, a p-hydroquinone sulfate obtained from a marine sponge, was shown to preferentially inhibit the α-family of eukaryotic DNA polymerases [169]. Purified metabolites from Okinawan marine sponge-and bivalve-associated microorganisms were screened for inhibitors of DNA polymerase.…”

Section: Dna Polymerasementioning

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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“…In 1994, Shioda et al. (14) found that halenaquinol sulfate, a p-hydroquinone sulfate obtained from a marine sponge, preferentially inhibits the eukaryotic DNA polymerase R-family.…”

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Novel Phenalenone Derivatives from a Marine-Derived Fungus Exhibit Distinct Inhibition Spectra against Eukaryotic DNA Polymerases

et al. 2002

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A number of compounds used for cancer chemotherapy exert their effects by inhibiting DNA replication. New inhibitors of DNA polymerases, therefore, could be potential candidates for new anti-cancer drugs. This study tested the effects of two phenalenone-skeleton-based compounds, which were isolated from a marine-derived fungus Penicillium sp., sculezonone-B (SCUL-B) and sculezonone-A (SCUL-A), upon DNA polymerase activity. Both compounds inhibited bovine DNA polymerases alpha and gamma, moderately affected the activity of DNA polymerase epsilon, and had almost no effect on HIV-reverse transcriptase and an E. coli DNA polymerase I Klenow fragment. Most notably, whereas SCUL-A inhibited pol beta (IC(50) = 17 microM), SCUL-B has only a weak influence upon this polymerase (IC(50) = 90 microM). Kinetic studies showed that inhibition of both DNA polymerases alpha and beta by either SCUL-A or SCUL-B was competitive with respect to dTTP substrate and noncompetitive with the template-primer. Whereas pol alpha inhibition by SCUL-B is competitive with respect to dATP, the inhibition by SCUL-A was found to be a mixed type with dATP substrate. The K(i) values of SCUL-B were calculated to be 1.8 and 6.8 microM for DNA polymerases alpha and gamma, respectively. The K(i) of DNA polymerase beta for SCUL-A was 12 microM and that for DNA polymerase alpha, 16 microM. Therefore, deletion of the OH-group at C12 enhanced inhibition of DNA polymerase beta. Since computational analyses of these two inhibitors revealed a remarkable difference in the distribution of negative electrostatic charge on the surface of molecules, we infer that different electrostatic charges might elicit different inhibition spectra from these two compounds.

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Differential inhibition of eukaryotic DNA polymerases by halenaquinol sulfate, a p‐hydroquinone sulfate obtained from a marine sponge

Cited by 10 publications

References 23 publications

Natural Products from Tongan Marine Organisms

Natural Products from Tongan Marine Organisms

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Novel Phenalenone Derivatives from a Marine-Derived Fungus Exhibit Distinct Inhibition Spectra against Eukaryotic DNA Polymerases

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