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Marine Drugs
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Search for New Drug Candidates and Their Lead Compounds from...
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Search for New Drug Candidates and Their Lead Compounds from Tunicates

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Synthesis and Medicinal Chemistry of Marine Natural Products".

Deadline for manuscript submissions: closed (21 March 2022) | Viewed by 24515

Special Issue Editors

Dr. Concetta Imperatore

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Guest Editor
Department of Pharmacy, School of Medicine and Surgery - University of Naples Federico II, Italy
Interests: marine natural products; isolation and stereostructural elucidation of bioactive secondary metabolites; design and synthesis of analogues of marine natural products; NMR spectroscopy; marine invertebrates
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marialuisa Menna

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Guest Editor
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano, 49 – 80131, Naples, Italy
Interests: natural products chemistry; NMR spectroscopy; small molecules structure elucidation; bioactive marine metabolites; synthetic and medicinal chemistry; chemical libraries; marine-inspired leads to drugs
Special Issues, Collections and Topics in MDPI journals
Dr. Marcello Casertano

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Guest Editor
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, Napoli, Italy
Interests: marine bioactive products; organic chemistry; NMR spectroscopy; stereostructural elucidation; quinone reactivity; antiinfective; antimicrobial; multitarget agents parasitic infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine ascidians (tunicates) hold a central role in the natural-product-based drug-discovery processes. With the over one thousands of new compounds isolated in the last 30 years, ascidians have established themselves as a valuable and heterogeneous source of new chemical scaffolds and pharmaceutically potent molecules, including clinically used compounds and preclinical leads. Moreover, the huge chemical diversity originating from the wealth of tunicates’ secondary metabolites has raised issues about the origin of these metabolites; it has been demonstrated that some of these compounds are made by symbiotic bacteria and not by the animals themselves. The therapeutic potential of ascidian-derived compounds and the biotechnological findings associated to their symbiotic origin still inspire scientists in the world, also linked to the possibility to use them as inspiration for a countless generation of synthetic drugs.

This Special Issue in “Search for New Drug Candidates and Their Lead Compounds from Tunicates” offers researchers the opportunity to publish their original works in a large number of fields. Thus, we invite marine scientists to submit papers based on natural products from tunicates and tunicate-associated microorganisms as well as synthetic marine-inspired compounds, useful for health and for environmental or biotechnological applications. Review papers that present up-to-date knowledge on bioactive compounds from marine tunicates useful for a specific therapeutic area (e.g., antitumor, antinflammatory, antimicrobial) or addressing the recent advances in ascidian symbiosis as it relates to natural products chemistry are also welcome.

Dr. Concetta Imperatore
Prof. Dr. Marialuisa Menna
Dr. Marcello Casertano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tunicates
  • Marine bioactive compounds
  • Structure-guided drug discovery
  • Structure elucidation
  • NPs analogue-inspired design
  • Bioactive substances
  • Organic synthesis

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Published Papers (5 papers)

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Research

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14 pages, 2017 KiB  
Article
Aqueous Extract of Sea Squirt (Halocynthia roretzi) with Potent Activity against Human Cancer Cells Acts Synergistically with Doxorubicin
by Yuting Zhu, Shanhao Han, Jianhui Li, Hongwei Gao and Bo Dong
Mar. Drugs 2022, 20(5), 284; https://doi.org/10.3390/md20050284 - 23 Apr 2022
Cited by 5 | Viewed by 3475
Abstract
Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment. Halocynthia roretzi, an edible marine sea squirt, has been demonstrated to have various kinds of biological activities, such [...] Read more.
Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment. Halocynthia roretzi, an edible marine sea squirt, has been demonstrated to have various kinds of biological activities, such as anti-diabetic, anti-hypertension, and enhancing immunity. In this study, we reported that aqueous extracts from the edible parts of H. roretzi presented significantly inhibiting the efficiency on HepG-2 cell viability. The separate mixed compound exhibited strong effects of inhibitory proliferation and induced apoptosis via the generation of ROS along with the concurrent loss of mitochondrial membrane potential on tumor cells. Furthermore, we found that there existed a significantly synergistic effect of the ascidian-extracted compound mixture with the anti-cancer drug doxorubicin. In the presence of the extracts from H. roretzi, the dose of doxorubicin at the cellular level could be reduced by a half dose. The extracts were further divided by semipreparative-HPLC and the active ingredients were identified as a mixture of fatty amide, which was composed of hexadecanamide, stearamide, and erucamide by UHPLC-MS/MS. Our results suggest that the potential toxicity of ascidian H. roretzi in tumor cells, and the compounds extracted from H. roretzi could be potentially utilized on functional nutraceuticals or as an adjunct in combination with chemotherapy. Full article
(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)
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13 pages, 2867 KiB  
Article
Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis
by Marcello Casertano, Massimo Genovese, Paolo Paoli, Alice Santi, Anna Aiello, Marialuisa Menna and Concetta Imperatore
Mar. Drugs 2022, 20(1), 65; https://doi.org/10.3390/md20010065 - 11 Jan 2022
Cited by 8 | Viewed by 2562
Abstract
The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline [...] Read more.
The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells. Full article
(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)
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25 pages, 3415 KiB  
Article
Diversity, Bioactivity Profiling and Untargeted Metabolomics of the Cultivable Gut Microbiota of Ciona intestinalis
by Caroline Utermann, Vivien A. Echelmeyer, Ernest Oppong-Danquah, Martina Blümel and Deniz Tasdemir
Mar. Drugs 2021, 19(1), 6; https://doi.org/10.3390/md19010006 - 24 Dec 2020
Cited by 12 | Viewed by 4092
Abstract
It is widely accepted that the commensal gut microbiota contributes to the health and well-being of its host. The solitary tunicate Ciona intestinalis emerges as a model organism for studying host–microbe interactions taking place in the gut, however, the potential of its gut-associated [...] Read more.
It is widely accepted that the commensal gut microbiota contributes to the health and well-being of its host. The solitary tunicate Ciona intestinalis emerges as a model organism for studying host–microbe interactions taking place in the gut, however, the potential of its gut-associated microbiota for marine biodiscovery remains unexploited. In this study, we set out to investigate the diversity, chemical space, and pharmacological potential of the gut-associated microbiota of C. intestinalis collected from the Baltic and North Seas. In a culture-based approach, we isolated 61 bacterial and 40 fungal strains affiliated to 33 different microbial genera, indicating a rich and diverse gut microbiota dominated by Gammaproteobacteria. In vitro screening of the crude microbial extracts indicated their antibacterial (64% of extracts), anticancer (22%), and/or antifungal (11%) potential. Nine microbial crude extracts were prioritized for in-depth metabolome mining by a bioactivity- and chemical diversity-based selection procedure. UPLC-MS/MS-based metabolomics combining automated (feature-based molecular networking and in silico dereplication) and manual approaches significantly improved the annotation rates. A high chemical diversity was detected where peptides and polyketides were the predominant classes. Many compounds remained unknown, including two putatively novel lipopeptides produced by a Trichoderma sp. strain. This is the first study assessing the chemical and pharmacological profile of the cultivable gut microbiota of C. intestinalis. Full article
(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)
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Review

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12 pages, 3587 KiB  
Review
Botryllus schlosseri as a Unique Colonial Chordate Model for the Study and Modulation of Innate Immune Activity
by Oron Goldstein, Edna Ayerim Mandujano-Tinoco, Tom Levy, Shani Talice, Tal Raveh, Orly Gershoni-Yahalom, Ayelet Voskoboynik and Benyamin Rosental
Mar. Drugs 2021, 19(8), 454; https://doi.org/10.3390/md19080454 - 9 Aug 2021
Cited by 6 | Viewed by 4029
Abstract
Understanding the mechanisms that sustain immunological nonreactivity is essential for maintaining tissue in syngeneic and allogeneic settings, such as transplantation and pregnancy tolerance. While most transplantation rejections occur due to the adaptive immune response, the proinflammatory response of innate immunity is necessary for [...] Read more.
Understanding the mechanisms that sustain immunological nonreactivity is essential for maintaining tissue in syngeneic and allogeneic settings, such as transplantation and pregnancy tolerance. While most transplantation rejections occur due to the adaptive immune response, the proinflammatory response of innate immunity is necessary for the activation of adaptive immunity. Botryllus schlosseri, a colonial tunicate, which is the nearest invertebrate group to the vertebrates, is devoid of T- and B-cell-based adaptive immunity. It has unique characteristics that make it a valuable model system for studying innate immunity mechanisms: (i) a natural allogeneic transplantation phenomenon that results in either fusion or rejection; (ii) whole animal regeneration and noninflammatory resorption on a weekly basis; (iii) allogeneic resorption which is comparable to human chronic rejection. Recent studies in B. schlosseri have led to the recognition of a molecular and cellular framework underlying the innate immunity loss of tolerance to allogeneic tissues. Additionally, B. schlosseri was developed as a model for studying hematopoietic stem cell (HSC) transplantation, and it provides further insights into the similarities between the HSC niches of human and B. schlosseri. In this review, we discuss why studying the molecular and cellular pathways that direct successful innate immune tolerance in B. schlosseri can provide novel insights into and potential modulations of these immune processes in humans. Full article
(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)
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21 pages, 1721 KiB  
Review
Marine Natural Products from Tunicates and Their Associated Microbes
by Chatragadda Ramesh, Bhushan Rao Tulasi, Mohanraju Raju, Narsinh Thakur and Laurent Dufossé
Mar. Drugs 2021, 19(6), 308; https://doi.org/10.3390/md19060308 - 26 May 2021
Cited by 38 | Viewed by 9013
Abstract
Marine tunicates are identified as a potential source of marine natural products (MNPs), demonstrating a wide range of biological properties, like antimicrobial and anticancer activities. The symbiotic relationship between tunicates and specific microbial groups has revealed the acquisition of microbial compounds by tunicates [...] Read more.
Marine tunicates are identified as a potential source of marine natural products (MNPs), demonstrating a wide range of biological properties, like antimicrobial and anticancer activities. The symbiotic relationship between tunicates and specific microbial groups has revealed the acquisition of microbial compounds by tunicates for defensive purpose. For instance, yellow pigmented compounds, “tambjamines”, produced by the tunicate, Sigillina signifera (Sluiter, 1909), primarily originated from their bacterial symbionts, which are involved in their chemical defense function, indicating the ecological role of symbiotic microbial association with tunicates. This review has garnered comprehensive literature on MNPs produced by tunicates and their symbiotic microbionts. Various sections covered in this review include tunicates’ ecological functions, biological activities, such as antimicrobial, antitumor, and anticancer activities, metabolic origins, utilization of invasive tunicates, and research gaps. Apart from the literature content, 20 different chemical databases were explored to identify tunicates-derived MNPs. In addition, the management and exploitation of tunicate resources in the global oceans are detailed for their ecological and biotechnological implications. Full article
(This article belongs to the Special Issue Search for New Drug Candidates and Their Lead Compounds from Tunicates)
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