Agelasine Diterpenoids and Cbl-b Inhibitory Ageliferins from the Coralline Demosponge Astrosclera willeyana

Abstract

An extract of the coralline demosponge Astrosclera willeyana inhibited the ubiquitin ligase activity of the immunomodulatory protein Cbl-b. The bioassay-guided separation of the extract provided ten active compounds, including three new N-methyladenine-containing diterpenoids, agelasines W–Y (1–3), a new bromopyrrole alkaloid, N(1)-methylisoageliferin (4), and six known ageliferin derivatives (5–10). The structures of the new compounds were elucidated from their spectroscopic and spectrometric data, including IR, HRESIMS, and NMR, and by comparison with spectroscopic data in the literature. While all of the isolated compounds showed Cbl-b inhibitory activities, ageliferins (4–10) were the most potent metabolites, with IC50 values that ranged from 18 to 35 μM.

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

“…Dagar et al [120] reported the one-pot synthesis of 3,4-diacylpyrrolo[1,2a]pyrazine by the reaction of an α-haloketone, azide, and N-substituted pyrrole-2-carboxaldehyde. This investigation reveals that only compound (38) showed potential in vitro anticancer activity against oral adenosquamous carcinoma and triple-negative human breast cancer cells in comparison with standard capecitabine. Olszewska et al [121] reported the synthesis and anticancer activity of trifluoromethyl 2-phosphonopyrrole against denocarcinomic human alveolar basal epithelial This study explains pyrrole analog (39) with trifluoro, phosphonyl, and phenyl group significantly inhibits cell cycle arrest at G1 and induces apoptosis in these cell line with IC 50 36.5 μM ± 1.80 and 27.9 μM ± 1.68.…”

“…Another pyrrole analog is ageliferin (5a), produced by sponges. First isolated from the caribbean and then okinawan marine sponges have potential antibacterial properties [ 38 ]. Similarly, nargenicin (5b) is isolated from Nocardia argeninensis found to be more effective against gram-positive bacteria [ 39 ] (Fig.…”

Marine natural products

“…437 Sponges of the genera Stylissa and Astroclera were the sources of stylissaol A 1023 and dimer N(1)-methylisoageliferin 1024, respectively. 438,439 Bromotyrosine-derived alkaloids were reported from a Greek Aplysina 1025-1028, Vietnamese Ecionemia acervus 1029 and an Egyptian Pseudoceratina arabica 1030, respectively. 421,440,441 Bromotyrosines are also commonly encountered in Suberea sponges.…”

“…Mero-sesquiterpenoids were reported from the genera Hippospongia 1042-1044, Dactylospongia 1045-1048 and Dysidea 1049, respectively, 416,[444][445][446][447] while there was only one report of sponge-derived mero-diterpenoids, from Astroclera willeyana 1050-1052. 439 Several reports of new sesquiterpenoids were published in 2021. New bisabolane-type sesquiterpenoids were obtained from Chinese Halichondria 1053-1060 and Plakortis 1061-1066 sponges, respectively, 448,449 and also from a North Sulawesi Axinella specimen 1067.…”

Recent Discoveries on Marine Organism Immunomodulatory Activities

“…The authors evaluated Cbl-b ubiquitin ligase inhibition using the Cbl-b biochemical assay. Of these metabolites, Ageliferins were the most potent in regard to inhibiting Cbl-b, with IC50 values ranging from 18 to 35 µM, compared to ageliferine diterpenoids, with IC50 > 50 µM [ 105 ].…”