Two Gracilioethers Containing a [2(5H)-Furanylidene]ethanoate Moiety and 9,10-Dihydroplakortone G: New Polyketides from the Caribbean Marine Sponge .

Gracilioether M () and 11,12-dihydrogracilioether M (), two polyketides with a [2(5H)-furanylidene]ethanoate moiety, along with known plakortone G () and its new naturally occurring derivative 9,10-dihydroplakortone G (), were isolated from the Caribbean marine sponge . The structures and absolute configuration of , , and were characterized by analysis of HRESIMS and NMR spectroscopic data, chemical derivatization, and side-by-side comparisons with published NMR data of related analogs. Compounds and and a mixture of and were evaluated for cytotoxicity against MCF-7 human breast cancer cells.

Marine Pharmacology in 2019-2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes.

Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of and Collected near Puerto Rico.

Plakortinic acids C () and D (), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges , underwent in vitro evaluation for antiplasmodial activity against the malaria parasite using a drug luminescence assay. Initial screening at 10 µM revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC of 5.

Kallopterolides A-I, a New Subclass of -Diterpenes Isolated from the Southwestern Caribbean Sea Plume .

Kallopterolides A-I (-), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume . The structures and relative configurations of - were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.

Isolation, Structural Analysis and Biological Activity Assays of Biselisabethoxanes A and B: Two Dissymmetric -Diterpenes from the Southwestern Caribbean Sea Gorgonian Coral .

Two novel dissymmetric diterpenoids, biselisabethoxanes A and B ( and ), were isolated from the hexane extracts of the gorgonian coral . Biselisabethoxane A () represents the first example of a marine-derived C dimer made of two distinct diterpene fragments, whereas biselisabethoxane B () is a fused heterodimer stemming from coupling of two amphilectane-based fragments. The structures of and were elucidated based on 1D and 2D NMR spectral data analysis.

Marine pharmacology in 2018: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.

The 2018 marine pharmacology literature review represents a continuation of the previous 11 reviews of a series initiated in 1998. Preclinical marine pharmacology research during 2018 was performed by investigators in 44 countries and contributed novel pharmacology for 195 marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 53 compounds, 73 compounds which presented antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 69 compounds were reported to show miscellaneous mechanisms of action which may contribute upon further investigation to several pharmacological classes.

Effect of the Agglomerate Geometry on the Effective Electrical Conductivity of a Porous Electrode.

The study of the microstructure of random heterogeneous materials, related to an electrochemical device, is relevant because their effective macroscopic properties, e.g., electrical or proton conductivity, are a function of their effective transport coefficients (ETC).

Plakortinic acids C and D: a pair of peroxide-polyketides possessing a rare 7,8-dioxatricyclo[4.2.2.0]dec-9-ene core from a two-sponge association of .

Plakortinic acids C () and D (), two unprecedented peroxide-polyketides with 7,8-dioxatricyclo[4.2.2.

Marine Pharmacology in 2016-2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The review of the 2016-2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016-2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes.

The Discreet Structural Diversity of Briarellins: DU8+ Guided Multiple Structure Revisions Yielded Two Unknown Structural Types.

Briarellins, a subset of C2-C11 cyclized cembranoids, were proposed to contain a C3-C14 ether or lactone bridge, similar to asbestinins. However, the total synthesis of the proposed structure of briarellin J revealed a misassignment. We revisited briarellins, computationally, with the help of a recently developed hybrid DFT/parametric method, DU8+, and revised the structures of briarellin C14-C3 ε-lactones to new structural types containing either a C14-C11 or C14-C12 lactone bridge.

A comparative study of small molecules targeting eIF4A.

The PI3K/Akt/mTOR kinase pathway is extensively deregulated in human cancers. One critical node under regulation of this signaling axis is eukaryotic initiation factor (eIF) 4F, a complex involved in the control of translation initiation rates. eIF4F-dependent addictions arise during tumor initiation and maintenance due to increased eIF4F activity-generally in response to elevated PI3K/Akt/mTOR signaling flux.

Marine Pharmacology in 2014-2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998-2013 reviews of this series. Research in marine pharmacology during 2014-2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research.

Effect of An Image Resolution Change on the Effective Transport Coefficient of Heterogeneous Materials.

Electrochemical electrodes comprise multiple phenomena at different scales. Several works have tried to model such phenomena using statistical techniques. This paper proposes a novel process to work with reduced size images to reconstruct microstructures with the Simulated Annealing method.

Searching for Small Molecules with an Atomic Sort.

The discovery of biologically active small molecules requires sifting through large amounts of data to identify unique or unusual arrangements of atoms. Here, we develop, test and evaluate an atom-based sort to identify novel features of secondary metabolites and demonstrate its use to evaluate novelty in marine microbial and sponge extracts. This study outlines an important ongoing advance towards the translation of autonomous systems to identify, and ultimately elucidate, atomic novelty within a complex mixture of small molecules.

Tracing MYC Expression for Small Molecule Discovery.

Our inability to effectively "drug" targets such as MYC for therapeutic purposes requires the development of new approaches. We report on the implementation of a phenotype-based assay for monitoring MYC expression in multiple myeloma cells. The open reading frame (ORF) encoding an unstable variant of GFP was engineered immediately downstream of the MYC ORF using CRISPR/Cas9, resulting in co-expression of both proteins from the endogenous MYC locus.

Target-Based Screening against eIF4A1 Reveals the Marine Natural Product Elatol as a Novel Inhibitor of Translation Initiation with Antitumor Activity.

The DEAD-box RNA helicase eIF4A1 carries out the key enzymatic step of cap-dependent translation initiation and is a well-established target for cancer therapy, but no drug against it has entered evaluation in patients. We identified and characterized a natural compound with broad antitumor activities that emerged from the first target-based screen to identify novel eIF4A1 inhibitors. We tested potency and specificity of the marine compound elatol versus eIF4A1 ATPase activity.

Synthesis and biological analysis of truncated calyculone H.

Herein, we report for the first time the design and linear synthesis of a truncated calyculone H () that lacks the telltale isopropyl/isopropylene groups, whereas the 12-membered macrocycle remains intact. Key steps for the framework of target molecule include allylic oxidation using SeO, Sharpless asymmetric epoxidation, Barbier zinc allylation, and ring-closing metathesis (RCM) reactions. A second truncated "calyculone-like" analogue, , with a different oxidation pattern around the ring was also synthesized following a similar strategy.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998-2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products.

ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A.

Activation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A.

Exploring the Sponge Consortium Plakortis symbiotica-Xestospongia deweerdtae as a Potential Source of Antimicrobial Compounds and Probing the Pharmacophore for Antituberculosis Activity of Smenothiazole A by Diverted Total Synthesis.

Fractionation of the bioactive CHCl-MeOH (1:1) extracts obtained from two collections of the sponge consortium Plakortis symbiotica-Xestospongia deweerdtae from Puerto Rico provided two new plakinidone analogues, designated as plakinidone B (2) and plakinidone C (3), as well as the known plakinidone (1), plakortolide F (4), and smenothiazole A (5). The structures of 1-5 were characterized on the basis of 1D and 2D NMR spectroscopic, IR, UV, and HRMS analysis. The absolute configurations of plakinidones 2 and 3 were established through chemical correlation methods, VCD/ECD experiments, and spectroscopic data comparisons.

Plakortinic Acids A and B: Cytotoxic Cycloperoxides with a Bicyclo[4.2.0]octene Unit from Sponges of the Genera Plakortis and Xestospongia.

Plakortinic acids A (2) and B (3), two polyketide endoperoxides with a bicyclo[4.2.0]octene unit, were isolated as minor constituents from the sponge-sponge symbiotic association Plakortis halichondrioides-Xestospongia deweerdtae, along with known epiplakinic acid F (1).

Reassignment of the absolute configuration of plakinidone from the sponge consortium using a combination of synthesis and a chiroptical approach.

Recent work by Wu et al. in connection with the first synthesis of the marine natural product plakinidone revealed that the most salient feature of its purported structure, a six-membered perlactone moiety, was in fact a five-membered lactone, i.e.

Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes.

The marine natural product (-)-8,15-diisocyano-11(20)-amphilectene (1), isolated from the Caribbean sponge Svenzea flava, was used as scaffold to synthetize five new products, all of which were tested against laboratory strains of Plasmodium falciparum and Mycobacterium tuberculosis H37Rv. The scaffold contains two isocyanide units that are amenable to chemical manipulation, enabling them to be elaborated into a small library of sulfur and selenium compounds. Although most of the analogs prepared were less potent than the parent compound, 5 was nearly equipotent showing IC50 values of 0.

Novel Very Long-Chain α-Methoxylated Δ5,9 Fatty Acids from the Sponge Asteropus niger Are Effective Inhibitors of Topoisomerases IB.

The novel fatty acids (2R,5Z,9Z)-2-methoxy-25-methyl-5,9-hexacosadienoic acid (1a) and (2R,5Z,9Z)-2-methoxy-24-methyl-5,9-hexacosadienoic acid (1b) were isolated in 80 % purity from the Caribbean sponge Asteropus niger by chloroform/methanol extraction followed by solvent partitioning and silica gel column chromatography. The compounds were characterized by utilizing a combination of gas chromatography-mass spectrometry, nuclear magnetic resonance, and circular dichroism. Acids 1a and 1b were not detected in the phospholipids (PtdCho and PtdIns) of the sponge, but rather as free FA and possibly in glycosylceramides.