Phallusiasterols A and B: Two New Sulfated Sterols from the Mediterranean Tunicate Phallusia fumigata and Their Effects as Modulators of the PXR Receptor

Abstract

Purification of the apolar extracts of the marine ascidian Phallusia fumigata, afforded two new sulfated sterols, phallusiasterols A (1) and B (2). The structures of the new compounds have been elucidated using mass spectrometry and NMR experiments. The effects of phallusiasterols A and B as modulators of pregnane-X-receptor (PXR) have been investigated. These studies revealed that phallusiasterol A induces PXR transactivation in HepG2 cells and stimulates the expression of the PXR target genes CYP3A4 and MDR1 in the same cell line. Molecular docking calculations suggested the theoretical binding mode of phallusiasterol A with hPXR and revealed that phallusiasterol A fitted well in the LBD of PXR.

Investigating the Antiparasitic Potential of the Marine Sesquiterpene Avarone, Its Reduced Form Avarol, and the Novel Semisynthetic Thiazinoquinone Analogue Thiazoavarone

“…Mar. Drugs 2020, 18 Successively, we selected both some of the developed methoxy thiazinoquinones, and some ad hoc synthesized new derivatives with the aim of investigating the antischistosomal properties of this chemical scaffold. Compounds were thus tested against larval stage, adult worm couples and eggs of the platyhelminth S. mansoni [14].…”

“…In the course of a systematic chemical study of the macroflora and macrofauna of the coastal area of Turkey in theİzmir Bay (Aegean Sea), as a part of our ongoing search for bioactive marine-derived metabolites as leads for drug discovery [15][16][17][18][19][20], we isolated from the sponge Dysidea avara (Schmidt, 1862) the known sesquiterpene quinone avarone (1), along with its reduced form avarol (3, Figure 2) [21][22][23]. A wide range of pharmacological properties have been reported for the redox couple avarone (1) and avarol (3) including anti-tumor [24][25][26], anti-inflammatory [27][28][29], anti-mutagenic [30], anti-bacterial [31,32], anti-viral [33,34], anti-oxidant [23,35], anti-platelet [28], anti-psoriatic [36] and anti-biofouling [37,38] activities.…”

Potential roles of nuclear receptors in mediating neurodevelopmental toxicity of known endocrine‐disrupting chemicals in ascidian embryos

“…The sensitivity of C. robusta FXR to sulfated steroids raises the possibility that an ancestral FXR, selective for invertebrate steroids or structurally related ligands, evolved in vertebrates to recognize bile salts. Furthermore, ascidians can produce steroids (Delrio, D’Istria, Milone, & Chieffi, ; Imperatore et al, ) and FXR might thus be the receptor responsible to respond to them and to intervene in adult sexual maturation. If this is true, there is a possibility that FXR in adult ascidians might bind some EDCs with a steroid‐like structure and alter their reproductive cycle.…”

In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products

“…Among them, a wide variety of often very complex molecules, originating from intra-and intermolecular cyclizations and/or rearrangements of the terpene chains to give unique polycyclic or macrocyclic structures, have been discovered [2,5,6]. In the course of our ongoing research program aimed at the search and characterization of new drug candidates of marine origin [7][8][9][10][11], a large group of new meroterpenes with different polycyclic skeletons but all featuring an unusual 1,1-dioxo-1,4-thiazine ring fused with the quinone moiety, i.e., aplidinones A and B, thiaplidiaquinones and conithiaquinones, were isolated from samples of Aplidium conicum [12][13][14]. The valuable antitumor activity shown by these compounds prompted us to further investigate the chemical and pharmacological features of this class of compounds [15].…”