Frondoplysins A and B, Unprecedented Terpene-Alkaloid Bioconjugates from Dysidea frondosa

Abstract

The chemical investigation of the marine sponge Dysidea frondosa discovered a pair of unprecedented bioconjugates that are composed of a meroterpene and an unusual psammaplysin alkaloid. The structures of frondoplysins A (1) and B (2) were characterized by analysis of HRMS and NMR data coupled with single-crystal X-ray diffraction. Frondoplysin A was found to be a potent inhibitor targeting protein-tyrosine phosphatase 1B (PTP1B) with an IC50 value of 0.39 μM.

Cytotoxic Psammaplysin Analogues from the Verongid Red Sea Sponge Aplysinella Species

“…Compounds possessing the rare dibrominated 1,6-dioxa-2-azaspiro [4.6]undeca-2,7,9-triene moiety (spirooxepinisoxazoline) are derived from bromotyrosine and are named psammaplysins [2][3][4][5][6][7][8][9][10], ceratinamides [9,11] and ceratinadins [12]. Compounds with the spirooxepinisoxazoline moiety were reported mainly from members of the Verongiida [2][3][4][5][6][7][8][9][10]12] with only two representatives from the order Dictyoceratida [11,13]. Psammaplysins' backbone consists of two dibrominated subunits, 8,10-dibromo-4-hydroxy-9-methoxy-1,6-dioxa-2-azaspiro [4.6]undeca-2,7,9-triene-3-carboxylic acid (subunit A) and 3-(4-(2-aminoethyl)-2,6-dibromophenoxy)propan-1-amine subunit (subunit B, moloka'iamine) [14], connected together through an amidic linkage between the carboxylic moiety (C-9) of the substituted spirooxepinisoxazoline unit and the terminal amino group at C-10 of the moloka'iamine ( Figure 1) to give the first reported compound of this class, psammaplysin A, (N-(3-(4-(2-aminoethyl)-2,6-dibromophenoxy)propyl)-8,10-dibromo-4-hydroxy-9-methoxy-1,6-dioxa-2azaspiro [4.6]undeca-2,7,9-triene-3-carboxamide) [2].…”

“…Psammaplysins' backbone consists of two dibrominated subunits, 8,10-dibromo-4-hydroxy-9-methoxy-1,6-dioxa-2-azaspiro [4.6]undeca-2,7,9-triene-3-carboxylic acid (subunit A) and 3-(4-(2-aminoethyl)-2,6-dibromophenoxy)propan-1-amine subunit (subunit B, moloka'iamine) [14], connected together through an amidic linkage between the carboxylic moiety (C-9) of the substituted spirooxepinisoxazoline unit and the terminal amino group at C-10 of the moloka'iamine ( Figure 1) to give the first reported compound of this class, psammaplysin A, (N-(3-(4-(2-aminoethyl)-2,6-dibromophenoxy)propyl)-8,10-dibromo-4-hydroxy-9-methoxy-1,6-dioxa-2azaspiro [4.6]undeca-2,7,9-triene-3-carboxamide) [2]. Interestingly, moloka'iamine (subunit B) and its substituted derivatives were reported from several Verongid sponges [9,[13][14][15], but there is no single report in the literature about the existence or isolation of the separated dibrominated spirooxepinisoxazoline moiety (subunit A). The substituted and dibrominated spirooxepinisoxazoline unit has been always associated with the moloka'iamine moiety via an amidic linkage [2][3][4][5][6][7][8][9][10][11][12][13].…”

“…Interestingly, moloka'iamine (subunit B) and its substituted derivatives were reported from several Verongid sponges [9,[13][14][15], but there is no single report in the literature about the existence or isolation of the separated dibrominated spirooxepinisoxazoline moiety (subunit A). The substituted and dibrominated spirooxepinisoxazoline unit has been always associated with the moloka'iamine moiety via an amidic linkage [2][3][4][5][6][7][8][9][10][11][12][13]. This can be explained by the necessity of such a combination as a defense tool for sponges against predators in the field.…”

“…Exceptionally, ceratinadins E and F possess two or three moloka'iamine subunits attached to the spirooxepinisoxazoline unit through amidic linkages [12]. Interestingly, frondoplysins A and B from Dysidea frondosa [13] possess an unusual meroterpene unit attached to the terminal amine of the psammaplysins [13].…”

Metabolites from marine invertebrates and their symbiotic microorganisms: molecular diversity discovery, mining, and application

“…In recent decades, research on the diversity of MNPs discovered from the South China Sea by other Chinese researchers has been well underway. These groundbreaking research efforts contributed to the discovery of a great number of novel and promising bioactive molecules usually from such sources as sponges Jiao et al 2019;Wang et al 2015b), corals Wu et al 2019), bryozoans (Yu et al 2015), and associated microorganisms (Cheng et al 2016;Nong et al 2016). Regarding the abundance of MNPs with diverse structures and a wealth of biological activities, we believe that only the proverbial "tip of the iceberg" has been explored from the South China Sea, and the resulting novel active metabolites with potential pharmacology applications are worthy of further exploration.…”