Manniosides G-J, New Ursane- and Lupane-Type Saponins from Schefflera mannii (Hook.f.) Harms.

Four previously unreported triterpenoid saponins named 3ß-hydroxy-23-oxours-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside G) (1), 23-O-acetyl-3ß-hydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside H) (2), ursolic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl] ester (mannioside I) (3), and 3ß-hydroxy-23-oxolup-20(29)-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside J) (4) were isolated as minor constituents from the EtOAc soluble fraction of the MeOH extract of the leaves of Schefflera mannii along with the known compounds 23-hydroxyursolic acid 28-O-ß-D-glucopyranosyl ester (5), ursolic acid 28-O-ß-D-glucopyranosyl ester (6), pulsatimmoside B (7) betulinic acid 28-O-[α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl] ester (8), 23-hydroxy-3-oxo-urs-12-en-28-oic acid (9), hederagenin (10), ursolic acid (11), betulinic acid (12), and lupeol (13). Their structures were elucidated by a combination of 1D and 2D NMR analysis and mass spectrometry. The MeOH extract, the EtOAc and n-BuOH fractions, and some of the isolated compounds were evaluated for their antibacterial activity against four bacteria: Staphylococcus aureus ATCC1026, Staphylococcus epidermidis ATCC 35984, Escherichia coli ATCC10536, and Klepsiella pnemoniae ATCC13882. They were also screened for their antioxidant properties, but no significant results were obtained.

Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro.

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 µM vs. 8.94 µM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 µM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 µM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

Green Synthesized sAuNPs as a Potential Delivery Platform for Cytotoxic Alkaloids.

The use of natural products as chemotherapeutic agents is well established. However, many are associated with undesirable side effects, including high toxicity and instability. Previous reports on the cytotoxic activity of pyrroloiminoquinones isolated from Latrunculid sponges against cancer cell lines revealed extraordinary activity at IC50 of 77nM for discorhabdins. Their general lack of selectivity against the cancer and normal cell lines, however, precludes further development. In this study, extraction of a South African Latrunculid sponge produced three known pyrroloiminoquinone metabolites (14-bromodiscorhabdin C (5), Tsitsikammamine A (6) and B (7)). The assignment of the structures was established using standard 1D and 2D NMR experiments. To mitigate the lack of selectivity, the compounds were loaded onto gold nanoparticles synthesized using the aqueous extract of a brown seaweed, Sargassum incisifolium (sAuNPs). The cytotoxicity of the metabolites alone, and their sAuNP conjugates, were evaluated together with the known anticancer agent doxorubicin and its AuNP conjugate. The compound-AuNP conjugates retained their strong cytotoxic activity against the MCF-7 cell line, with >90% of the pyrroloiminoquinone-loaded AuNPs penetrating the cell membrane. Loading cytotoxic natural products onto AuNPs provides an avenue in overcoming some issues hampering the development of new anticancer drugs.

Identification and in vitro anti-esophageal cancer activity of a series of halogenated monoterpenes isolated from the South African seaweeds Plocamium suhrii and Plocamium cornutum.

Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R∗,4S∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R∗,4S∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1). Compounds 1-6 showed greater cytotoxicity in this assay as compared to the known anticancer drug cisplatin.

Synthesis and photophysical properties of tetra- and octasubstituted phosphorous oxide triazatetrabenzcorrole photosensitizers.

The synthesis of phosphorous oxide triazatetrabenzcorroles (TBC) tetra- (9, 11) or octa- (13) substituted on the ring with halogenated functional groups is reported. The complexes are not aggregated in dimethylsulfoxide (DMSO) and show solubility in solvents such as pyridine. The Q band absorption spectra of the complexes are red-shifted compared to unsubstituted PTBC. The latter complex shows a large triplet lifetime (1.7 milliseconds), higher than for MPc derivatives. The chlorinated derivatives show good triplet yields (Phi(T) approximately 0.46 and 0.36) and relatively long lifetimes (256 and 452 microseconds), respectively, for 11 and 13.

Halogenated monoterpene aldehydes from the South African marine alga Plocamium corallorhiza.

Four new halogenated monoterpene aldehydes (1-4) have been isolated from the South African marine red alga Plocamium corallorhiza, along with the known compounds 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene (5) and 1,4,8-tribromo-3,7-dichloro-3,7-dimethyl-1E,5E-octadiene (10). The structures of the new compounds were determined by interpretation of their spectroscopic data and synthesis and mass spectrometric analysis of their pentafluorobenzyloxime (PFBO) derivatives.

Pyrroloiminoquinone and related metabolites from marine sponges.

This review presents the structure, biological activity, biosynthetic studies and, where applicable, references to syntheses of 81 marine alkaloids containing either tetra-, hexa- or octa-hydrogenated variants of pyrrolo[4,3,2-de]quinoline, pyrrolo[4,3,2-de]pyrrolo[2,3-h]quinoline and pyrido[2,3-h]pyrrolo[4,3,2-de]quinoline core skeletons. The literature describing the isolation of pyrroloiminoquinones, and related metabolites, from marine sponges is littered with taxonomic inconsistencies and recent efforts to clarify the taxonomy of the sponges that produce this group of metabolites are discussed.

The identification of the UV degradants of melatonin and their ability to scavenge free radicals.

Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2-. and particularly the.OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC-MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2-. generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC-MS results show that the degradants of melatonin are 6-hydroxymelatonin and N1-acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)-induced superoxide generation compared to non-irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.

Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.

An examination of organic extracts of four new species of South African latrunculid sponges, Tsitsikamma pedunculata, T. favus, Latrunculia bellae, and Strongylodesma algoaensis, yielded 13 known and eight new pyrroloiminoquinone alkaloids, 3-dihydro-7,8-dehydrodiscorhabdin C (4), 14-bromo-3-dihydro-7,8-dehydrodiscorhabdin C (5), discorhabdin V (6), 14-bromo-1-hydroxydiscorhabdin V (7), tsitsikammamine A N-18 oxime (10), tsitsikammamine B N-18 oxime (11), 1-methoxydiscorhabdin D (12), and 1-aminodiscorhabdin D (13). Standard spectroscopic methods provided the structures of the pyrroloiminoquinone metabolites, while chiral GC-MS analysis of the acylated ozonolysis products of 21 confirmed the stereochemistry of the l-histidine residue in this compound. The anticancer activity of 20 pyrroloiminoquinone compounds was explored in the HCT-116 cancer cell line screen, and the DNA intercalation of the tsitsikammamines, together with their ability to cleave DNA through topoisomerase I inhibition, is discussed.