Table of Contents

Abstract: Owing to the increasing importance of aquaculture to compensate for the progressive worldwide reduction of natural fish and to the fact that several fish farming plants often suffer from heavy financial losses due to the development of infections caused by microbial pathogens, including multidrug resistant bacteria, more environmentally-friendly strategies to control fish infections are urgently needed to make the aquaculture industry more sustainable. The aim of this review is to briefly present the typical fish farming diseases and their threats and discuss the present state of chemotherapy to inactivate microorganisms in fish farming plants as well as to examine the new environmentally friendly approaches to control fish infection namely phage therapy and photodynamic antimicrobial therapy.

Abstract: Because of the highly unique structures of marine natural products, there are many examples of structures that were originally proposed based on spectral analyses but later proven incorrect. In many cases, the total syntheses of the originally proposed structures of marine natural products has confirmed their incorrectness and the subsequent total syntheses of the newly proposed structures proved the revised structures. This review will show such cases appearing after 2005 and demonstrate how the true structures were elucidated.

Abstract: Background: We used 2-deoxy-2-[¹⁸F] fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with advanced and/or metastatic soft tissue sarcoma (STS) undergoing therapy with Ecteinascidin-743 (ET-743, Trabectedin, Yondelis^TM). Patients and Methods: The pilot study included nine patients with metastatic STS receiving a minimum of one cycle of treatment with trabectedin. Patients were examined using PET prior to onset of therapy and after completion of one or three cycles of trabectedin. Restaging according to Response Evaluation Criteria in Solid Tumours (RECIST) was performed in parallel using computed tomography (CT) and/or magnetic resonance imaging (MRI) and served for reference. Results: Clinical outcome of nine evaluable patients was as follows: one patient with partial remission (PR), three patients with stable disease (SD), and five patients with progressive disease (PD). A more than 40% decrease of the standardized uptake value (SUV) of sequential PET examination could be demonstrated for the responding patient (PR), whereas patients with SD or PD showed a stable SUV, but no increase in SUV. Conclusion: To our knowledge, this is the first small series of patients being treated with trabectedin and monitored using sequential PET imaging demonstrating SUV stabilization in nearly all monitored patients.

Abstract: A marine sulfate-reducing bacterium SRB-22 was isolated by means of the agar shake dilution method and identified as Desulfovibrio desulfuricans by morphological, physiological and biochemical characteristics and 16S rDNA analysis. In the bioassay, its extract showed broad-spectrum antimicrobial activity using the paper disc agar diffusion method. This isolate showed a different antimicrobial profile than either ampicillin or nystatin and was found to produce at least eight antimicrobial components by bioautography. Suitable fermentation conditions for production of the active constituents were determined to be 28 day cultivation at 25 °C to 30 °C with a 10% inoculation ratio. Under these conditions, the SRB-22 was fermented, extracted and chemically investigated. So far an antimicrobial compound, mono-n-butyl phthalate, and an inactive compound, thymine, have been isolated and characterized.

Abstract: Two new brominated selinane sesquiterpenes, 1-bromoselin-4(14),11-diene (1) and 9-bromoselin-4(14),11-diene (2), one known cadinane sesquiterpene, cadalene (3), and four known selinane sesquiterpenes, α-selinene (4), β-selinene (5), β-dictyopterol (6), and cyperusol C (7), were isolated from a sample of marine brown alga Dictyopteris divaricata collected off the coast of Yantai (China). Their structures were established by detailed MS and NMR spectroscopic analysis, as well as comparison with literature data.

Abstract: Crude extracts and column fractions from the red algae Asparagopsis taxiformis and A. armata from the Strait of Messina (Italy) were screened for the production of antimicrobial compounds. Extracts from both species revealed remarkable antiprotozoal activity against Leishmania, revealing such algae as a great source of natural antiprotozoal products.

Abstract: Diatoms are one of the main primary producers in aquatic ecosystems and occupy a vital link in the transfer of photosynthetically-fixed carbon through aquatic food webs. Diatoms produce an array of biologically-active metabolites, many of which have been attributed as a form of chemical defence and may offer potential as candidate marine drugs. Of considerable interest are molecules belonging to the oxylipin family which are broadly disruptive to reproductive and developmental processes. The range of reproductive impacts includes; oocyte maturation; sperm motility; fertilization; embryogenesis and larval competence. Much of the observed bioactivity may be ascribed to disruption of intracellular calcium signalling, induction of cytoskeletal instability and promotion of apoptotic pathways. From an ecological perspective, the primary interest in diatom-oxylipins is in relation to the potential impact on energy flow in planktonic systems whereby the reproductive success of copepods (the main grazers of diatoms) is compromised. Much data exists providing evidence for and against diatom reproductive effects; however detailed knowledge of the physiological and molecular processes involved remains poor. This paper provides a review of the current state of knowledge of the mechanistic impacts of diatom-oxylipins on marine invertebrate reproduction and development.

Abstract: S-Adenosylmethionine (AdoMet) is a key biochemical co-factor whose proximate metabolites include methylated macromolecules (e.g., nucleic acids, proteins, phospholipids), methylated small molecules (e.g., sterols, biogenic amines), polyamines (e.g., spermidine, spermine), ethylene, and N-acyl-homoserine lactones. Marine organisms produce numerous AdoMet metabolites whose novel structures can be regarded as lead compounds for anti-infective drug design.

Abstract: Two new jaspamide derivatives 2 and 3, together with the parent compound jaspamide (1) have been isolated from the marine sponge Jaspis splendens collected in Kalimantan (Indonesia). The structures of the new compounds were unambiguously elucidated based on 1D and 2D NMR spectral data, mass spectrometry and comparison with jaspamide (1). The new derivatives inhibited the growth of mouse lymphoma (L5178Y) cell line in vitro with IC₅₀ values of <0.1 μg/mL.

Abstract: A new cyclic diamine, 1,5-diazacyclohenicosane (1), was isolated from samples of the marine sponge Mycale sp. collected at Lamu Island (Kenya). Its structure was determined by a combination of spectroscopic techniques, including (+)-HRESIMS and 1D and 2D NMR spectroscopy. The compound displayed cytotoxicity at the μM level against three human tumor cell lines.

Abstract: The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m²) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

Abstract: 2-(2’,4’-Dibromophenoxy)-4,6-dibromophenol isolated from the marine sponge Dysidea granulosa (Bergquist) collected off the coast of Lakshadweep islands, Indian Ocean, exhibited potent and broad spectrum in-vitro antibacterial activity, especially against methicillin resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), vancomycin resistant Enterococci (VRE), vancomycin sensitive Enterococci (VSE) and Bacillus spp. Minimal inhibitory concentration (MIC) was evaluated against 57 clinical and standard strains of Gram positive and Gram negative bacteria. The observed MIC range was 0.117-2.5 μg/mL against all the Gram positive bacteria and 0.5-2 μg/mL against Gram negative bacteria. The in-vitro antibacterial activity observed was better than that of the standard antibiotic linezolid, a marketed anti-MRSA drug. The results establish 2-(2’,4’-dibromophenoxy)-4,6-dibromophenol, as a potential lead molecule for anti-MRSA and anti-VRE drug development.

Abstract: Two new briarane-related diterpenoids, designated as excavatoids E (1) andF (2), were isolated from the cultured octocoral Briareum excavatum. The structures ofcompounds 1 and 2 were established on the basis of extensive spectral data analysis. Briaranes 1 and 2 were found to exhibit moderate inhibitory effects on elastase release by human neutrophils.