The chemistry and biology of guanidine secondary metabolites

Sea cucumbers are a class of marine invertebrates and a source of food and drug. Numerous microorganisms are associated with sea cucumbers. Seventy-eight genera of bacteria belonging to 47 families in four phyla, and 29 genera of fungi belonging to 24 families in the phylum Ascomycota have been cultured from sea cucumbers. Sea-cucumber-associated microorganisms produce diverse secondary metabolites with various biological activities, including cytotoxic, antimicrobial, enzyme-inhibiting, and antiangiogenic activities. In this review, we present the current list of the 145 natural products from microorganisms associated with sea cucumbers, which include primarily polyketides, as well as alkaloids and terpenoids. These results indicate the potential of the microorganisms associated with sea cucumbers as sources of bioactive natural products.

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Natural Products in Polyclad Flatworms

Marine Drugs ◽

10.3390/md19020047 ◽

2021 ◽

Vol 19 (2) ◽

pp. 47

Author(s):

Justin M. McNab ◽

Jorge Rodríguez ◽

Peter Karuso ◽

Jane E. Williamson

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Marine Invertebrates ◽

Symbiotic Bacteria ◽

Chemical Defences ◽

Number Of Species ◽

Bioactive Secondary Metabolites ◽

Potential Sources ◽

Polyclad Flatworms

Marine invertebrates are promising sources of novel bioactive secondary metabolites, and organisms like sponges, ascidians and nudibranchs are characterised by possessing potent defensive chemicals. Animals that possess chemical defences often advertise this fact with aposematic colouration that potential predators learn to avoid. One seemingly defenceless group that can present bright colouration patterns are flatworms of the order Polycladida. Although members of this group have typically been overlooked due to their solitary and benthic nature, recent studies have isolated the neurotoxin tetrodotoxin from these mesopredators. This review considers the potential of polyclads as potential sources of natural products and reviews what is known of the activity of the molecules found in these animals. Considering the ecology and diversity of polyclads, only a small number of species from both suborders of Polycladida, Acotylea and Cotylea have been investigated for natural products. As such, confirming assumptions as to which species are in any sense toxic or if the compounds they use are biosynthesised, accumulated from food or the product of symbiotic bacteria is difficult. However, further research into the group is suggested as these animals often display aposematic colouration and are known to prey on invertebrates rich in bioactive secondary metabolites.

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Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates

Molecules ◽

10.3390/molecules26071898 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1898

Author(s):

Fauzia Izzati ◽

Mega Ferdina Warsito ◽

Asep Bayu ◽

Anggia Prasetyoputri ◽

Akhirta Atikana ◽

...

Keyword(s):

Natural Products ◽

Bioactive Compounds ◽

Marine Natural Products ◽

Biological Function ◽

Marine Invertebrates ◽

Biological Activities ◽

Structural Diversity ◽

Chemical Diversity ◽

Soft Corals ◽

High Chemical

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007–2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.

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Synthetic Approaches to Tetracyclic Pyrrole Imidazole Marine Alkaloids

Natural Product Communications ◽

10.1177/1934578x1300800722 ◽

2013 ◽

Vol 8 (7) ◽

pp. 1934578X1300800 ◽

Cited By ~ 1

Author(s):

Takuya Imaoka ◽

Makoto Iwata ◽

Takafumi Akimoto ◽

Kazuo Nagasawa

Keyword(s):

Natural Products ◽

Total Synthesis ◽

Anticancer Activity ◽

Biological Activities ◽

Structural Complexity ◽

Marine Alkaloids ◽

Ring Systems ◽

Agonistic Activity ◽

Synthetic Approaches

Oroidin derived pyrrole imidazole marine alkaloids (PIAs) are attractive targets for synthetic organic chemists because of their structural complexity and diversity as well as their interesting biological activities. A number of efforts have been carried out to develop strategies for the synthesis of these natural products. Members of PIAs ( eg., 2-7) which contain tetracyclic ring systems possessing characteristic cyclic guanidine or urea moieties show significant biological activities including anticancer activity and agonistic activity against the adrenoceptor. In this review investigations of the total synthesis of the representative tetracyclic PIAs dibromophakellin (2) and dibromophakellstatin (3) are described.

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Marine Terpenic Endoperoxides

Marine Drugs ◽

10.3390/md19120661 ◽

2021 ◽

Vol 19 (12) ◽

pp. 661

Author(s):

Irene Torres-García ◽

Josefa L. López-Martínez ◽

Manuel Muñoz-Dorado ◽

Ignacio Rodríguez-García ◽

Miriam Álvarez-Corral

Keyword(s):

Total Synthesis ◽

Marine Invertebrates ◽

Biological Activities ◽

Structural Features ◽

Naturally Occurring ◽

Organic Extracts ◽

Pharmaceutical Uses ◽

Potential Use ◽

Dioxane Ring

Organic extracts of marine invertebrates, mainly sponges, from seas all over the world are well known for their high in vitro anticancer and antibiotic activities which make them promising sources of compounds with potential use as pharmaceutical leads. Most of the structures discovered so far have a peculiar structural feature in common: a 1,2-dioxane ring. This is a highly reactive heterocycle that can be considered as an endoperoxide function. Together with other structural features, this group could be responsible for the strong biological activities of the substances present in the extracts. Numerous research programs have focused on their structural elucidation and total synthesis since the seventies. As a consequence, the number of established chiral centres and the similarity between different naturally occurring substances is increasingly higher. Most of these compounds have a terpenoid nature, mainly diterpene and sesterterpene, with several peculiar structural features, such as the loss of one carbon atom. Although there are many reviews dealing with the occurrence of marine peroxides, their activities, or potential pharmaceutical uses, no one has focused on those having a terpene origin and the endoperoxide function. We present here a comprehensive review of these compounds paying special attention to their structural features and their biological activity.

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Insights into the Diversity of Secondary Metabolites of Planktothrix Using a Biphasic Approach Combining Global Genomics and Metabolomics

10.20944/preprints201906.0310.v1 ◽

2019 ◽

Author(s):

Sanrda Kim Tiam ◽

Muriel Gugger ◽

Justine Demay ◽

Severine Le Manach ◽

Charlotte Duval ◽

...

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Biological Activities ◽

Chemical Diversity ◽

Chemical Structures ◽

Metabolite Profiles ◽

Ancient Lineage ◽

Major Bottleneck ◽

Different Strains ◽

Slow Growing

Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and a proliﬁc source of natural products with diverse chemical structures and potent biological activities and toxicities. The chemical identiﬁcation of these compounds remains a major bottleneck. Strategies that can prioritize the most proliﬁc strains and novel compounds are of great interest. Here, we combine chemical analysis and genomics to investigate the chemodiversity of secondary metabolites based on their pattern of distribution within some cyanobacteria. Planktothrix being a cyanobacterial genus known to form blooms worldwide and to produce a broad spectrum of toxins and other bioactive compounds, we applied this combined approach on four closely related strains of Planktothrix. The chemical diversity of the metabolites produced by the four strains was evaluated using an untargeted metabolomics strategy with high-resolution LC-MS. Metabolite proﬁles were correlated with the potential of metabolite production identified by genomics for the different strains. Although, the Planktothrix strains present a global similarity in term biosynthetic cluster gene for microcystin, aeruginosin and prenylagaramide for example, we found remarkable strain-specific chemo-diversity. Only few of the chemical features were common to the four studied strains. Additionally, the MS/MS data were analyzed using Global Natural Products Social Molecular Networking (GNPS) to identify molecular families of the same biosynthetic origin. In conclusion, we present an efﬁcient integrative strategy for elucidating the chemical diversity of a given genus and link the data obtained from analytical chemistry to biosynthetic genes of cyanobacteria.

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Total Synthesis of Phorbazole B

Molecules ◽

10.3390/molecules25204848 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4848

Author(s):

Yngve Guttormsen ◽

Magnus E. Fairhurst ◽

Sunil K. Pandey ◽

Johan Isaksson ◽

Bengt Erik Haug ◽

...

Keyword(s):

Natural Products ◽

High Resolution ◽

Secondary Metabolites ◽

Total Synthesis ◽

Cancer Cells ◽

Marine Sponge ◽

Inhibitory Activity ◽

Late Stage ◽

Nmr Techniques

Phorbazoles are polychlorinated heterocyclic secondary metabolites isolated from a marine sponge and several of these natural products have shown inhibitory activity against cancer cells. In this work, a synthesis of the trichlorinated phorbazole B using late stage electrophilic chlorination was developed. The synthesis relied on the use of an oxazole precursor, which was protected with an iodine in the reactive 4-position, followed by complete chlorination of all pyrrole positions. Attempts to prepare phorbazole A and C, which contain a 3,4-dichlorinated pyrrole, were unsuccessful as the desired chlorination pattern on the pyrrole could not be obtained. The identities of the dichlorinated intermediates and products were determined using NMR techniques including NOESY/ROESY, 1,1-ADEQUATE and high-resolution CLIP-HSQMBC.

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Marine Natural Products as A Source of Drug Leads against Respiratory Viruses: Structural and Bioactive Diversity

Current Medicinal Chemistry ◽

10.2174/0929867327666201026150105 ◽

2020 ◽

Vol 27 ◽

Author(s):

Tian-Tian Sun ◽

Hua-Jie Zhu ◽

Fei Cao

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Marine Natural Products ◽

Biological Activities ◽

Respiratory Viruses ◽

Antiviral Activities ◽

Syncytial Virus ◽

Effective Drugs ◽

Drug Leads ◽

Novel Structures

: Respiratory viruses, including influenza virus, respiratory syncytial virus, coronavirus, et al., have seriously threatened the human health. For example, the outbreak of severe acute respiratory syndrome coronavirus, SARS, affected a large number of countries around the world. Marine organisms, which could produce secondary metabolites with novel structures and abundant biological activities, are an important source for seeking effective drugs against respiratory viruses. This report reviews marine natural products with activities against respiratory viruses, the emphasis of which was put on structures and antiviral activities of these natural products. This review has described 167 marine-derived secondary metabolites with activities against respiratory viruses published during 1981 to 2019. Altogether 102 references are cited in this review article.

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Total synthesis of bryostatin 3

Science ◽

10.1126/science.abb7271 ◽

2020 ◽

Vol 368 (6494) ◽

pp. 1007-1011 ◽

Cited By ~ 4

Author(s):

Barry M. Trost ◽

Youliang Wang ◽

Andreas K. Buckl ◽

Zhongxing Huang ◽

Minh H. Nguyen ◽

...

Keyword(s):

Natural Products ◽

Total Synthesis ◽

Marine Natural Products ◽

Biological Activities ◽

Step Count ◽

Total Syntheses ◽

Linear Sequence ◽

Wide Range

Bryostatins are a family of 21 complex marine natural products with a wide range of potent biological activities. Among all the 21 bryostatins, bryostatin 3 is structurally the most complex. Whereas nine total syntheses of bryostatins have been achieved to date, bryostatin 3 has only been targeted once and required the highest number of steps to synthesize (43 steps in the longest linear sequence and 88 total steps). Here, we report a concise total synthesis of bryostatin 3 using 22 steps in the longest linear sequence and 31 total steps through a highly convergent synthetic plan by the use of highly atom-economical and chemoselective transformations in which alkynes played a major role in reducing step count.

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A Review of the Secondary Metabolites From the Marine Sponges of the Genus Aaptos

Natural Product Communications ◽

10.1177/1934578x20951439 ◽

2020 ◽

Vol 15 (9) ◽

pp. 1934578X2095143

Author(s):

Qianqian He ◽

Shuang Miao ◽

Na Ni ◽

Yuqing Man ◽

Kaikai Gong

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Natural Product ◽

Chemical Ecology ◽

Marine Natural Products ◽

Organic Molecules ◽

Biological Activities ◽

Marine Sponges ◽

Marine Natural Product ◽

Natural Product Research

Marine sponges, which belong to the phylum Porifera (Metazoa), are considered the single best source of marine natural products. Among them, members of the genus Aaptos are attractive targets for marine natural product research owing to their abundant biogenetic ability to produce aaptamine derivatives. Apart from aaptamine alkaloids, there are also reports of other compounds from Aaptos sponges. This work reviews the secondary metabolites isolated from Aaptos species from 1982 to 2020, with 46 citations referring to 62 compounds (47 for aaptamines and 15 for others). The emphasis is placed on the structure of the organic molecules, relevant biological activities, chemical ecology aspects, and biosynthesis studies, which are described in the classifications of aaptamines and other compounds in the order of the published year.

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