Novel Adociaquinone Derivatives from the Indonesian Sponge Xestospongia sp.

Fei He,Arlette Longeon,Amandine Bescond,Nadège Loaëc,Marie-Lise Bourguet-Kondracki,Laurent Meijer,Brent Copp,Linh Mai

doi:10.3390/md13052617

Abstract

Seven new adociaquinone derivatives, xestoadociaquinones A (1a), B (1b), 14-carboxy-xestoquinol sulfate (2) and xestoadociaminals A–D (3a, 3c, 4a, 4c), together with seven known compounds (5–11) were isolated from an Indonesian marine sponge Xestospongia sp. Their structures were elucidated by extensive 1D and 2D NMR and mass spectrometric data. All the compounds were evaluated for their potential inhibitory activity against eight different protein kinases involved in cell proliferation, cancer, diabetes and neurodegenerative disorders as well as for their antioxidant and antibacterial activities.

Highlights

Marine sponges of the genus Xestospongia have proved to be an extremely rich source of secondary metabolites with unprecedented molecular structures and various bioactivities [1,2,3]
The HMBC spectrum revealed the correlations between the proton at δH 7.70 (H-1) and the carbons at δC 123.2 (C-2), 145.2 (C-8) and 149.7 (C-7), and between the proton at δH 1.51 (H3-20) and the carbons at δC 32.3 (C-5), 38.1 (C-6), 149.7 (C-7) and 153.8 (C-19)
8.19 (H-11) and the carbon at δC 72.4 (C-13), between the exchangeable proton at δH 6.79 (OH-13) and the carbons at δC 44.1 (C-24), 72.4 (C-13), and 137.8 (C-12) and between the other exchangeable proton at δH 7.03 (OH-23) to the carbons at δC 44.1 (C-24) and 87.5 (C-23) (Figure 5). These correlations again identified the presence of a pyrrolidine ring fused between the dioxothiazine and quinone rings of an adociaquinone-type molecule, but in contrast to ring fusion to C-16 in 3a–d, fusion in compound 4 was at C-13

Summary

Introduction

Marine sponges of the genus Xestospongia have proved to be an extremely rich source of secondary metabolites with unprecedented molecular structures and various bioactivities [1,2,3]. Adocia- [4], halena- [5] and xesto-quinone [6] are the three main quinone-type skeletons identified from sponges of the genus Xestospongia sp. Among the most significant compounds, adociaquinones A and B, first isolated from the sponge Adocia sp. By our group led to the isolation of a series of halenaquinone-type compounds, including xestosaprol C methylacetal, 3-ketoadociaquinones A and B, tetrahydrohalenaquinones A and B, halenaquinol sulfate, halenaquinone and orhalquinone [8]. Bio-guided fractionation of the extract led to the isolation of seven new adociaquinone derivatives 1a–4c, together with seven known compounds, adociaquinone A 5 and B 6 [4], secoadociaquinones A 7 and B 8, 15-chloro-14-hydroxyxestoquinone 9, 14-chloro-15-hydroxyxestoquinone [7] and xestoquinol sulfate [9] (Figure 1). We describe the isolation and structural elucidation of the new compounds as well as their biological activities

Results and Discussion

General Experimental Procedures

Extraction and Isolation

Protein Kinase Assays

Antibacterial Assay

Antioxidant Assay