Aging research aims at developing therapies that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to slow aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce a wide variety of bioactive secondary metabolites; however, those from the Southwest of the Indian Ocean are much less studied, especially regarding anti-aging activities. In this study, the microbial diversity of the marine sponge Scopalina hapalia was investigated by metagenomic analysis. Twenty-six bacterial and two archaeal phyla were recovered from the sponge, of which the Proteobacteria phylum was the most abundant. In addition, 30 isolates from S. hapalia were selected and cultivated for identification and secondary metabolites production. The selected isolates were affiliated to the genera Bacillus, Micromonospora, Rhodoccocus, Salinispora, Aspergillus, Chaetomium, Nigrospora and unidentified genera related to the family Thermoactinomycetaceae. Crude extracts from selected microbial cultures were found to be active against seven clinically relevant targets (elastase, tyrosinase, catalase, sirtuin 1, Cyclin-dependent kinase 7 (CDK7), Fyn kinase and proteasome). These results highlight the potential of microorganisms associated with a marine sponge from Mayotte to produce anti-aging compounds. Future work will focus on the isolation and the characterization of bioactive compounds.

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer’s disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J (1) and sinularone K (2), one phospholipid 1-O-octadecyl-2-pentanoyl-sn-glycero-3-phosphocholine (3) and one lysophospholipid 1-O-(3-methoxy-tetradecanoyl)-sn-glycero-3-phosphocholine (4) alongside with known lysophospholipids (5 and 6), alkylglycerols (7–10), epidioxysterols (11 and 12) and diketopiperazines (13 and 14). The structure elucidation of the new metabolites (1–4) was determined by detailed spectroscopic analysis, including 1D and 2D NMR as well as mass spectrometry. Molecular networking was also explored to complement classical investigation and unravel the chemical classes within this species. GNPS analysis provided further information on potential metabolites with additional bioactive natural compounds predicted.

Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications.

CDK7 and FynB protein kinases have been recognized as relevant targets for cancer and brain diseases treatment due to their pivotal regulatory roles in cellular functions such as cell cycle and neural signal transduction. Several studies demonstrated that the inhibition of these proteins could be useful in altering the onset or progression of these diseases. Based on bioassay-guided approach, the extract of the marine sponge Lendenfeldia chondrodes (Thorectidae), which exhibited interesting kinase inhibitory activities, was fractionated. The investigation led to the isolation of five known 1-5 and one new 6 polybrominated diphenyl ethers (PBDEs). Their structure elucidation was established based on spectroscopic data (NMR and HRMS) and comparison with literature data.