An Aminopyrimidone and Aminoimidazoles Alkaloids from the Rodrigues Calcareous Marine Sponge Ernsta naturalis.

A chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Ernsta naturalis collected in Rodrigues (Mauritius) based on a molecular networking dereplication strategy highlighted one novel aminopyrimidone alkaloid compound, ernstine A (1), seven new aminoimidazole alkaloid compounds, phorbatopsins D-E (2, 3), calcaridine C (4), naamines H-I (5, 7), naamidines J-K (6, 8), along with the known thymidine (9). Their structures were established by spectroscopic analysis (1D and 2D NMR spectra and HRESIMS data). To improve the investigation of this unstudied calcareous marine sponge, a metabolomic study by molecular networking was conducted. The isolated molecules are distributed in two clusters of interest. Naamine and naamidine derivatives are grouped together with ernstine in the first cluster of twenty-three molecules. Phorbatopsin derivatives and calcaridine C are grouped together in a cluster of twenty-one molecules. Interpretation of the MS/MS spectra of other compounds of these clusters with structural features close to the isolated ones allowed us to propose a structural hypothesis for 16 compounds, 5 known and 11 potentially new.

Osirisynes G-I, New Long-Chain Highly Oxygenated Polyacetylenes from the Mayotte Marine Sponge Haliclona sp.

Chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Haliclona sp. collected in Mayotte highlighted three new long-chain highly oxygenated polyacetylenes, osirisynes G-I (1-3) together with the known osirisynes A (4), B (5), and E (6). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS and MS/MS data. All compounds were evaluated on catalase and sirtuin 1 activation and on CDK7, proteasome, Fyn kinase, tyrosinase, and elastase inhibition. Five compounds (1; 3-6) inhibited proteasome kinase and two compounds (5-6) inhibited CDK7 and Fyn kinase. Osirisyne B (5) was the most active compound with IC50 on FYNB kinase, CDK7 kinase, and proteasome inhibition of 18.44 µM, 9.13 µM, and 0.26 µM, respectively.

New Antimalarial and Antimicrobial Tryptamine Derivatives from the Marine Sponge Fascaplysinopsis reticulata.

Chemical study of the CH2Cl2-MeOH (1:1) extract of the sponge Fascaplysinopsis reticulata collected in Mayotte highlighted three new tryptophan derived alkaloids, 6,6'-bis-(debromo)-gelliusine F (1), 6-bromo-8,1'-dihydro-isoplysin A (2) and 5,6-dibromo-8,1'-dihydro-isoplysin A (3), along with the synthetically known 8-oxo-tryptamine (4) and the three known molecules from the same family, tryptamine (5), (E)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (6) and (Z)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (7). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their antimicrobial and their antiplasmodial activities. Regarding antimicrobial activities, the best compounds are (2) and (3), with minimum inhibitory concentration (MIC) of 0.01 and 1 µg/mL, respectively, towards Vibrio natrigens, and (5), with MIC values of 1 µg/mL towards Vibrio carchariae. In addition the known 8-oxo-tryptamine (4) and the mixture of the (E)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (6) and (Z)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (7) showed moderate antiplasmodial activity against Plasmodium falciparum with IC50 values of 8.8 and 8.0 µg/mL, respectively.

Unguiculin A and Ptilomycalins E-H, Antimalarial Guanidine Alkaloids from the Marine Sponge Monanchora unguiculata.

Chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Monanchora unguiculata collected in Madagascar highlighted five new compounds, one acyclic guanidine alkaloid, unguiculin A (1) and four pentacyclic alkaloids, ptilomycalins E-H (2-5), along with four known compounds: crambescidin 800 (6) and crambescidin 359 (7), crambescidic acid (8), and fromiamycalin (9). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. The new ptilomycalin E (2) and the mixture of the new ptilomycalins G (4) and H (5) showed promising cytotoxicity against KB cells with IC50 values of 0.85 and 0.92 µM, respectively. Ptilomycalin F (3) and fromiamycalin (9) exhibited promising activity against Plasmodium falciparum with IC50 values of 0.23 and 0.24 µM, respectively.

Polybrominated diphenyl ethers isolated from the marine sponge Lendenfeldia chondrodes collected in Mayotte.

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.

Cytotoxic Metabolites from Calophyllum tacamahaca Willd.: Isolation and Detection through Feature-Based Molecular Networking.

Isocaloteysmannic acid (1), a new chromanone, was isolated from the leaf extract of the medicinal species Calophyllum tacamahaca Willd. along with 13 known metabolites belonging to the families of biflavonoids (2), xanthones (3-5, 10), coumarins (6-8) and triterpenes (9, 11-14). The structure of the new compound was characterized based on nuclear magnetic resonance (NMR), high-resolution electrospray mass spectrometry (HRESIMS), ultraviolet (UV) and infrared (IR) data. Its absolute configuration was assigned through electronic circular dichroism (ECD) measurements. Compound (1) showed a moderate cytotoxicity against HepG2 and HT29 cell lines, with IC50 values of 19.65 and 25.68 µg/mL, respectively, according to the Red Dye method. Compounds 7, 8 and 10-13 exhibited a potent cytotoxic activity, with IC50 values ranging from 2.44 to 15.38 µg/mL, against one or both cell lines. A feature-based molecular networking (FBMN) approach led to the detection of a large amount of xanthones in the leaves extract, and particularly analogues of the cytotoxic isolated xanthone pyranojacareubin (10).

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae).

Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4'-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4'-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC50 values ≤ 5 µg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).

Antiplasmodial, anti-chikungunya virus and antioxidant activities of 64 endemic plants from the Mascarene Islands.

Vector-borne diseases cause more than 1 million deaths annually. The research into new medicines is urgent, especially as there is currently no specific treatment. In this study, the authors have selected 64 endemic plants from the Mascarene Islands based on their endemism, their medicinal use and their registration in the French Pharmacopeia to evaluate the antiplasmodial, anti-chikungunya and antioxidant activities. The list of these 64 plants including their local name, population, data of collection and voucher number are available in the Supporting Information. Forty active extracts were identified from the 38 species: 22 responded positively to the antiplasmodial activity, 8 to the anti-chikungunya activity and 8 to the antioxidant activity. Six plants demonstrated high antiplasmodial activity (concentration inhibiting 50% of parasitic growth (IC50) <5 µg/mL): Casearia coriaceae, Monimia rotundifolia, Poupartia borbonica, Psiadia retusa, Vernonia fimbrillifera and Zanthoxylum heterophyllum; and five showed high anti-chikungunya activity (IC50<20 µg/mL): Aphloia theiformis, Stillingia lineata, Croton mauritianus, Indigofera ammoxylum, and Securinega durissima. Eight plants displayed an important antioxidant activity, with values of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) or oxygen Radical Absorbance Capacity (ORAC) >2000 µM of Trolox equivalent per mg/mL of extract: Bertiera borbonica, Erythroxylon laurifolium, Erythroxylon sideroxyloides, I. ammoxylum, P. borbonica, Scolopia heterophylla, Sophora denudata, and Terminalia bentzoe. Some data obtained tend to corroborate the reported traditional use of the plant, such as Z. heterophyllum (antiplasmodial), A. theiformis (anti-chikungunya), and E. laurifolium (antioxidant).