Antifungal Amphidinol 18 and Its 7‑Sulfate Derivative from the Marine Dinoflagellate <i>Amphidinium carterae</i>

Two new polyketides of the amphidinol family, amphidinol 18 (AM18, <b>1</b>) and its corresponding 7-sulfate derivative (AM19, <b>2</b>), have been isolated from the MeOH extract of the dinoflagellate <i>Amphidinium carterae</i>. Structure elucidation of the two polyoxygenated molecules has been accomplished by extensive use of spectroscopic and spectrometric techniques. AM18 exhibited antifungal activity against <i>Candida albicans</i> at 9 μg/mL

Sequestered Fulvinol-Related Polyacetylenes in <i>Peltodoris atromaculata</i>

The Mediterranean dorid nudibranch <i>Peltodoris atromaculata</i> that had been collected while feeding on <i>Haliclona fulva</i> was shown to sequester long-chain fulvinol-like polyacetylene metabolites (compounds <b>2</b>–<b>5</b>) from the prey. They were isolated along with previously reported bromorenierins from the diethyl ether extracts of both the mollusk and the sponge. Their structures were elucidated by NMR spectroscopy and tandem FABMS analysis. Compound <b>5</b> exhibited in vitro growth inhibitory effects against the SKMEL-28 melanoma cell line

Identification and Synthesis of Mycalol Analogues with Improved Potency against Anaplastic Thyroid Carcinoma Cell Lines

The marine metabolite mycalol (<b>1</b>) has a specific inhibitory activity on cells of anaplastic thyroid carcinoma (ATC), a very aggressive and rare cancer that does not have effective conventional therapy. In this study, we describe six new related analogues (<b>2</b>–<b>7</b>) that differ in the length of the terminal alkyl residue and the presence of acetate or 3<i>S</i>-hydroxybutyrate (3S)-3HB as a substituent at C-19. Despite the structural analogies, some of the new members were significantly more cytotoxic than <b>1</b> on cell lines derived from human ATC. Structures inclusive of the 2′<i>R</i>,3<i>R</i>,4<i>S</i>,7<i>R</i>,8<i>S</i>,19<i>R</i> absolute configuration were assigned to <b>2</b>–<b>7</b> on the basis of detailed spectroscopic analysis, synthesis of different isomers, and application of ECD and Mosher’s methods. This work led to the identification of mycalol-578 (<b>3</b>) as the most potent analogue, with an IC₅₀ of 2.3 μM on FRO cells

Potential of Lipid Biosynthesis under Heterotrophy in the Marine Diatom <i>Cyclotella cryptica</i>

Despite the theoretical high productivity, microalgae-based oil production is not economically sustainable due to the high cost of photoautotrophic cultures. Heterotrophic growth is a suitable economic alternative to overcoming light dependence and climatic/geographic fluctuations. Here we report data about growth performance, biomass production, and lipid composition of the marine diatom Cyclotella cryptica, chosen as a model strain for biodiesel production in heterothrophy. A repeated-batch process of heterotrophic cultivation has also been investigated to assess the robustness and phenotypic stability. The process consisting of six constant cycle repetitions was carried out for 42 days and led to an average dry biomass production of 1.5 ± 0.1 g L–1 of which 20% lipids composed of 60% triglycerides, 20% phospholipids. and 20% glycolipids. The major fatty acids were C16:0 (∼26%), C16:1 ω-7 (∼57%), and C20:5 ω-3 (∼12%), with a significant reduction in the unsaturated fatty acids in comparison to other microalgae grown in heterotrophy. Fatty acids were differently distributed among the glycerolipid classes, and the lipid composition was used to compare the potential properties of C. cryptica oil with traditional vegetable biofuels

Dinoflagellate-Related Amphidinolides from the Brazilian Octocoral <i>Stragulum bicolor</i>

Benthic cnidarians are colonial marine animals that host a rich population of associated and symbiotic microorganisms. In a recent paper we described for the first time the isolation of amphidinolide P (<b>1</b>) from the Brazilian octocoral <i>Stragulum bicolor.</i> Amphidinolides and similar compounds had been previously reported only from dinoflagellates of the genus <i>Amphidinium</i>; thus the presence of <b>1</b> in the invertebrate opens intriguing questions on the role and occurrence of these molecules in marine ecosystems. Here we report the identification of four further amphidinolides from the same soft coral, including the known amphidinolide T1 (<b>2</b>) and the new analogues here named amphidinolides C4 (<b>3</b>), B8 (<b>4</b>), and B9 (<b>5</b>). The chemical structures have been elucidated mainly by extensive study of spectroscopic data. Cytotoxic activities of <b>3</b> and <b>4</b> were evaluated against the colon adenocarcinoma cell line HCT-116

<i>In Vitro</i> Pharmacological and Toxicological Effects of Norterpene Peroxides Isolated from the Red Sea Sponge <i>Diacarnus erythraeanus</i> on Normal and Cancer Cells

Eight cyclic peroxide norterpenoids, compounds <b>1</b>–<b>8</b>, have been isolated and characterized from the Red Sea sponge <i>Diacarnus erythraeanus</i>, including two new norsesterterpene derivatives (<b>3</b>, <b>4</b>). Among these metabolites, (−)-muqubilin A (<b>5</b>) (nine cell lines analyzed) and the new compounds <b>3</b> and <b>4</b> (seven cell lines analyzed) displayed mean IC₅₀ growth inhibitory concentrations <i>in vitro</i> of <10 μM, while the remaining compounds (<b>1</b>, <b>6</b>–<b>8</b>) were inactive in these cancer cell lines. Compound <b>5</b> displayed no selectivity between normal and cancer cells in terms of <i>in vitro</i> growth inhibition. Quantitative video microscopy analysis carried out on (−)-muqubilin A-treated cells validated the data obtained by means of the MTT colorimetric assay, while flow cytometry analysis revealed ROS production but no induction of apoptosis in cancer cells

BODIPY-Based Analogue of the TREM2-Binding Molecular Adjuvant Sulfavant A, a Chemical Tool for Imaging and Tracking Biological Systems

Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A (1), Sulfavant R (2), and Sulfavant S (3), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene moiety (Me4-BODIPY). The fluorescent derivative, named PB-SULF A (4), preserving the biological activity of Sulfavants, opens the way to chemical biology and cell biology experiments to better understand the interactions with cellular and in vivo organ targets and to improve our comprehension of complex molecular mechanisms underlying the not fully understood ligand-induced TREM2 activity