An analysis of the interaction of marine sponge-derived bioactive compounds with type 2 diabetes mellitus targets DPP-4 and PTP1B.

Type 2 diabetes is a medical condition involving elevated blood glucose levels resulting from impaired or improper insulin utilization. As the number of type 2 diabetes cases increases each year, there is an urgent need to develop novel drugs having new targets and/or complementing existing therapeutic protocols. In this regard, marine sponge-derived compounds hold great potential due to their potent biological activity and structural diversity.

Repairing plasma membrane damage in regulated necrotic cell death.

The plasma membrane performs a central role in maintaining cellular homeostasis and viability by acting as a semi-permeable barrier separating the cell from its surroundings. Under physiological conditions, it is constantly exposed to different kinds of stress, such as from pore-forming proteins/toxins and mechanical activity, that compromises its integrity resulting in cells developing various ways to cope with these dangers to survive. These plasma membrane repair mechanisms are initiated by the rapid influx of extracellular Ca ions and are thus hinged on the activity of various Ca-binding proteins.

Ferroptotic pores induce Ca fluxes and ESCRT-III activation to modulate cell death kinetics.

Ferroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca is a hallmark of ferroptosis that precedes complete bursting of the cell.

Theonellamide A, a marine-sponge-derived bicyclic peptide, binds to cholesterol in aqueous DMSO: Solution NMR-based analysis of peptide-sterol interactions using hydroxylated sterol.

Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides isolated from the marine sponge Theonella sp. The inclusion of cholesterol (Chol) or ergosterol in the phosphatidylcholine membrane is known to significantly enhance the membrane affinity for theonellamide A (TNM-A). We have previously revealed that TNM-A stays in a monomeric form in dimethylsulfoxide (DMSO) solvent systems, whereas the peptide forms oligomers in aqueous media.

Sterol-dependent membrane association of the marine sponge-derived bicyclic peptide Theonellamide A as examined by H NMR.

Theonellamide A (TNM-A) is an antifungal bicyclic dodecapeptide isolated from a marine sponge Theonella sp. Previous studies have shown that TNM-A preferentially binds to 3β-hydroxysterol-containing membranes and disrupts membrane integrity. In this study, several H NMR-based experiments were performed to investigate the interaction mode of TNM-A with model membranes.

Membrane permeabilizing action of amphidinol 3 and theonellamide A in raft-forming lipid mixtures.

Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the dinoflagellate Amphidinium klebsii and the sponge Theonella spp., respectively. Both of these metabolites have been demonstrated to interact with membrane lipids ultimately resulting in a compromised bilayer integrity.

Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores.

Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marine sponge Theonella sp. These peptides specifically bind to 3β-hydroxysterols, resulting in 1,3-β-D-glucan overproduction and membrane damage in yeasts. The inclusion of cholesterol or ergosterol in phosphatidylcholine membranes significantly enhanced the membrane affinity of theonellamide A (TNM-A) because of its direct interaction with 3β-hydroxyl groups of sterols.

Direct and stereospecific interaction of amphidinol 3 with sterol in lipid bilayers.

Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol.

Interaction between the marine sponge cyclic peptide theonellamide A and sterols in lipid bilayers as viewed by surface plasmon resonance and solid-state (2)H nuclear magnetic resonance.

Theonellamides (TNMs) are members of a distinctive family of antifungal and cytotoxic bicyclic dodecapeptides isolated from the marine sponge Theonella sp. Recently, it has been shown that TNMs recognize 3β-hydroxysterol-containing membranes, induce glucan overproduction, and damage cellular membranes. However, to date, the detailed mode of sterol binding at a molecular level has not been determined.

A bioactive sesquiterpene from Bixa orellana.

A dichloromethane extract of the air-dried leaves of Bixa orellana afforded ishwarane 1, phytol 2, polyprenol 3, and a mixture of stigmasterol 4a and sitosterol 4b by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy. Compound 1 at three doses (25, 50, and 100 mg/kg BW) was tested for prophylactic, gastrointestinal motility, analgesic, hypoglycemic, and antimicrobial potentials.