Marine Natural Products: A Themed Issue in Honor of Professor John Blunt and Professor Murray Munro

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 14114

Special Issue Editors


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Guest Editor
Department of Aquatic Bioscience, The University of Tokyo, Tokyo 1138657, Japan

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Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA
Interests: natural products chemistry; chemical biology of natural products; NMR spectroscopy
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Retired Branch Chief, Natural Products Branch, National Cancer Institute, Frederick, MD 21702-1201, USA
Interests: marine metabolites as drug leads and clinical candidates; marine microbiology; bioinformatics
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Special Issue Information

Dear Colleagues,

This Special Issue of Marine Drugs is dedicated to Professors John W. Blunt and Murray H. G. Munro, two pioneering New Zealand natural products researchers from the University of Canterbury who have made tremendous contributions to advance the science and support the marine natural products research community at large. They have successfully worked together throughout their careers as a collaborative pair of scientists, combining their individual talents, interests, and insights in a productive and synergistic manner that exemplifies the true spirit of scientific cooperation. Drs. Munro and Blunt are superb natural product discovery and structural elucidation chemists who also incorporated sophisticated biological screening and characterization studies as a key component of their scientific efforts. Their joint research program is focused largely on the chemistry of New Zealand marine invertebrates and microbes, and it has resulted in the discovery of a large number of new metabolites, many of which display unique molecular architectures or potent biological properties. In addition to marine organisms, John and Murray have also investigated the chemistry of assorted terrestrial fungi, and they are well known in the natural products community for their pioneering advances in the development and application of micro-scale NMR-based dereplication methods for selecting and prioritizing natural product samples. Memorable discoveries by this productive team of researchers include diverse compounds such as the dischorhabdins, mycalamides, variolins, cladobotric acids, spiromycins, pteratides, isohomohalichondrin B, pateamine, coproverdine, and spiro-mamakone A.

As a complement to the many new bioactive compounds they identified, Drs. Blunt and Munro also focused on the biological characterization and subsequent development of marine metabolites as potential therapeutic agents. Notable efforts in this regard include extensive preclinical studies of variolin B, which were done in conjunction with the Spanish pharmaceutical company PharmaMar SA. The discovery by Murray and John of a new source of halichondrin B in the New Zealand marine sponge Lissodendoryx sp., coupled with the productive utilization of this resource, ultimately provided the U.S. National Cancer Institute (NCI) with sufficient material to conduct critical in vivo efficacy studies. Halichondrin B was thus shown to be a powerful new anticancer agent, and these findings, along with synthetic access to the natural product and a series of analogues pioneered by the Kishi group at Harvard, paved the way for the successful development of the approved anticancer drug Erubilin (Halaven) by Eisai Pharmaceuticals.

In addition to their memorable natural product discovery and development efforts, John Blunt and Murray Munro made many valuable contributions to support and advance the broad field of marine natural products. They initiated, maintained, and expanded the well-known MarinLit database that researchers world-wide use as an invaluable tool in their own marine natural product programs. This database of publications in the marine natural products field grew to include not only references and structures, but other important features such as spectroscopic data, biological activity, and information on the source organism as well as the collection location. MarinLit was initiated in 1985 and maintained by John and Murray until 2013, when it was acquired by the Royal Society of Chemistry. They also took over, from the late D. John Faulkner, the annual Marine Natural Products review published in the journal Natural Products Reports, and served as coordinating authors from 2003–2018. Virtually everyone involved in marine natural products studies has utilized and benefitted from these vital community resources that Murray and John put so much time, effort, and thought into.

Murray Munro received his Ph.D. from the University of Otago, New Zealand, and did post-doctoral studies with Professor Sir Alan Battersby at the University of Liverpool before starting his independent academic career at the University of Canterbury in 1968. John Blunt earned his Ph.D. at the University of Canterbury, was a postdoctoral fellow at the University of Wisconsin, USA, and Oxford University, U.K., and in 1970, he returned to the University of Canterbury to begin his faculty career in the Department of Chemistry. In 1976, Murray and John joined together to launch a program for the discovery of bioactive natural products from marine sources. This highly successful collaborative endeavor was maintained for the remainder of their research careers. John and Murray have received numerous honors and distinctions throughout the years, including being joint recipients of the Paul J. Scheuer Award from the 2008 Gordon Research Conference on Marine Natural Products and the Norman R. Farnsworth Research Achievement Award in 2011 from the American Society of Pharmacognosy.

When one thinks of marine natural product studies in New Zealand, the contributions of John Blunt and Murray Munro immediately come to mind. They pioneered the initial chemistry efforts, and quickly showed that marine organisms in New Zealand waters are a rich source of novel structural diversity and important biologically active metabolites. They produced an impressive legacy of important natural product discoveries and also mentored many of the New Zealand scientists who continue to engage in natural product studies. I have had the pleasure to know and work with both John and Murray since my early days at the NCI. From the very beginning of our long-lasting interactions, I was impressed with their diligence, productivity, and collaborative approach to research. They demonstrated an expansive knowledge of natural product chemistry, spectroscopy, and related disciplines that strongly influenced my own research efforts. Their outstanding cooperative research program and their commitment and service to the greater marine natural products community has helped shape and inform contemporary natural products studies. The Munro and Blunt research team exemplifies the true spirit of collaborative science, with a diversity in interests and a commitment to excellence in the field of natural products that we can all be proud of. Cheers to Murray Munro and John Blunt for the well-deserved honor and recognition of a Special Issue of Marine Drugs dedicated to their careers and accomplishments in advancing the study and development of marine natural products.

Prof. Dr. Shigeki Matsunaga
Dr. Kirk R. Gustafson
Dr. David J. Newman
Guest Editors

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Published Papers (6 papers)

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Editorial

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2 pages, 148 KiB  
Editorial
The Benefits of Collaboration
by John W. Blunt and Murray H. G. Munro
Mar. Drugs 2023, 21(2), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/md21020065 - 19 Jan 2023
Viewed by 1035
Abstract
We have been very humbled by the decision of the Marine Drugs Editors to honor us with a Special Issue dedicated to our efforts over the past 50 years, as well as their invitation to write a guest editorial for this issue [...] [...] Read more.
We have been very humbled by the decision of the Marine Drugs Editors to honor us with a Special Issue dedicated to our efforts over the past 50 years, as well as their invitation to write a guest editorial for this issue [...] Full article

Research

Jump to: Editorial

18 pages, 2712 KiB  
Article
New Theonellapeptolides from Indonesian Marine Sponge Theonella swinhoei as Anti-Austerity Agents
by Jabal Rahmat Haedar, Agustinus Robert Uria, Subehan Lallo, Dya Fita Dibwe and Toshiyuki Wakimoto
Mar. Drugs 2022, 20(11), 661; https://0-doi-org.brum.beds.ac.uk/10.3390/md20110661 - 25 Oct 2022
Cited by 5 | Viewed by 2107
Abstract
We reported three new members of the theonellapeptolide family from theonellapeptolide II series, namely theonellapeptolides IIb (1), IIa (2), IIc (3), and three known members—IId (4), IIe (5), and Id (6)—from [...] Read more.
We reported three new members of the theonellapeptolide family from theonellapeptolide II series, namely theonellapeptolides IIb (1), IIa (2), IIc (3), and three known members—IId (4), IIe (5), and Id (6)—from Kodingarengan marine sponge Theonella swinhoei collected in Makassar, Indonesia. The structures of tridecadepsipeptides 13, including the absolute configurations of their amino acids, were determined by the integrated NMR and tandem MS analyses followed by Marfey’s analysis. To the best of our knowledge, 1 and 2 are the first theonellapeptolide-type compounds to have a valine residue with D configuration at residue position 6. The isolated theonellapeptolide-type compounds 16 showed selective cytotoxic activity against human pancreatic MIA PaCa-2 cancer cells in a nutrient-deprived medium. Among them, the most potent preferential cytotoxicity was observed in new theonellapeptolide IIc (3) and known IId (4), IIe (5), and Id (6). Full article
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14 pages, 3534 KiB  
Article
The Chemically Highly Diversified Metabolites from the Red Sea Marine Sponge Spongia sp.
by Chi-Jen Tai, Atallah F. Ahmed, Chih-Hua Chao, Chia-Hung Yen, Tsong-Long Hwang, Fang-Rong Chang, Yusheng M. Huang and Jyh-Horng Sheu
Mar. Drugs 2022, 20(4), 241; https://0-doi-org.brum.beds.ac.uk/10.3390/md20040241 - 30 Mar 2022
Cited by 5 | Viewed by 2424
Abstract
A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3β,5α-diol-6,5-olide (3); and an α,β-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4 [...] Read more.
A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3β,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3β,5α-diol-6,5-olide (3); and an α,β-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2’-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 19 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities. Full article
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13 pages, 3847 KiB  
Article
Hidden Diversity in an Antarctic Algal Forest: Metabolomic Profiling Linked to Patterns of Genetic Diversification in the Antarctic Red Alga Plocamium sp.
by Andrew J. Shilling, Sabrina Heiser, Charles D. Amsler, James B. McClintock and Bill J. Baker
Mar. Drugs 2021, 19(11), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/md19110607 - 27 Oct 2021
Cited by 12 | Viewed by 2406
Abstract
The common Antarctic red alga Plocamium sp. is rich in halogenated monoterpenes with known anticancer and antimicrobial properties and extracts of Plocamium sp. have strong ecological activity in deterring feeding by sympatric herbivores. Plocamium sp. collected near Anvers Island, Antarctica showed a high [...] Read more.
The common Antarctic red alga Plocamium sp. is rich in halogenated monoterpenes with known anticancer and antimicrobial properties and extracts of Plocamium sp. have strong ecological activity in deterring feeding by sympatric herbivores. Plocamium sp. collected near Anvers Island, Antarctica showed a high degree of secondary metabolite diversity between separate individuals. GC/MS results revealed 15 different combinations of metabolites (chemogroups) across individuals, which were apparent at 50% or greater Bray–Curtis similarity and also clearly distinguishable by eye when comparing chromatographic profiles of the secondary metabolomes. Sequencing of the mitochondrial cox1 gene revealed six distinct haplotypes, of which the most common two had been previously reported (now referred to as Haplotypes 1 and 2). With the exception of one individual, three of the chemogroups were only produced by individuals in Haplotype 1. All the other 12 chemogroups were produced by individuals in Haplotype 2, with five of these chemogroups also present in one of the four new, less common haplotypes that only differed from Haplotype 2 by one base pair. The functional relevance of this metabolomic and genetic diversity is unknown, but they could have important ecological and evolutionary ramifications, thus potentially providing a foundation for differential selection. Full article
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10 pages, 983 KiB  
Article
Agelasine Diterpenoids and Cbl-b Inhibitory Ageliferins from the Coralline Demosponge Astrosclera willeyana
by Wei Jiang, Dongdong Wang, Brice A. P. Wilson, Unwoo Kang, Heidi R. Bokesch, Emily A. Smith, Antony Wamiru, Ekaterina I. Goncharova, Donna Voeller, Stanley Lipkowitz, Barry R. O’Keefe and Kirk R. Gustafson
Mar. Drugs 2021, 19(7), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/md19070361 - 24 Jun 2021
Cited by 6 | Viewed by 2633
Abstract
An extract of the coralline demosponge Astrosclera willeyana inhibited the ubiquitin ligase activity of the immunomodulatory protein Cbl-b. The bioassay-guided separation of the extract provided ten active compounds, including three new N-methyladenine-containing diterpenoids, agelasines W–Y (13), a new [...] Read more.
An extract of the coralline demosponge Astrosclera willeyana inhibited the ubiquitin ligase activity of the immunomodulatory protein Cbl-b. The bioassay-guided separation of the extract provided ten active compounds, including three new N-methyladenine-containing diterpenoids, agelasines W–Y (13), a new bromopyrrole alkaloid, N(1)-methylisoageliferin (4), and six known ageliferin derivatives (510). The structures of the new compounds were elucidated from their spectroscopic and spectrometric data, including IR, HRESIMS, and NMR, and by comparison with spectroscopic data in the literature. While all of the isolated compounds showed Cbl-b inhibitory activities, ageliferins (410) were the most potent metabolites, with IC50 values that ranged from 18 to 35 μM. Full article
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10 pages, 1965 KiB  
Article
Structure Elucidation of Calyxoside B, a Bipolar Sphingolipid from a Marine Sponge Cladocroce sp. through the Use of Beckmann Rearrangement
by Kenji Sugawara, Hiroshi Watarai, Yuji Ise, Hisayoshi Yokose, Yasuhiro Morii, Nobuhiro Yamawaki, Shigeru Okada and Shigeki Matsunaga
Mar. Drugs 2021, 19(6), 287; https://0-doi-org.brum.beds.ac.uk/10.3390/md19060287 - 21 May 2021
Cited by 3 | Viewed by 2427
Abstract
Marine sponges are an excellent source of biologically active secondary metabolites. We focus on deep-sea sponges for our discovery study. A marine sponge Cladocroce sp. exhibited cytotoxic activity in the bioactivity screening. From this sponge a previously unreported cytotoxic glycosphingolipid, calyxoside B, was [...] Read more.
Marine sponges are an excellent source of biologically active secondary metabolites. We focus on deep-sea sponges for our discovery study. A marine sponge Cladocroce sp. exhibited cytotoxic activity in the bioactivity screening. From this sponge a previously unreported cytotoxic glycosphingolipid, calyxoside B, was isolated and the structure of this compound was elucidated by analyses of MS and NMR spectra and chemical derivatization. We converted the ketone in the middle of a long aliphatic chain into an oxime to which was applied Beckmann rearrangement to afford two positional isomers of amides. The products were subjected to acidic hydrolysis followed by LC-MS analysis, permitting us to assign unequivocally the position of the ketone. Calyxoside B shows cytotoxicity against HeLa cells with an IC50 value of 31 µM and also weakly stimulated the production of cytokines in mice. Full article
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