Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

Eight secondary metabolites (1 to 8) were isolated from a marine sponge, a marine alga and three terrestrial plants collected in Australia and subsequently chemically characterised. Here, these natural product-derived compounds were screened for in vitro-anthelmintic activity against the larvae and adult stages of Haemonchus contortus (barber’s pole worm)—a highly pathogenic parasitic nematode of ruminants. Using an optimised, whole-organism screening system, compounds were tested on exsheathed third-stage larvae (xL3s) and fourth-stage larvae (L4s). Anthelmintic activity was initially evaluated on these stages based on the inhibition of motility, development and/or changes in morphology (phenotype). We identified two compounds, 6-undecylsalicylic acid (3) and 6-tridecylsalicylic acid (4) isolated from the marine brown alga, Caulocystis cephalornithos, with inhibitory effects on xL3 and L4 motility and larval development, and the induction of a “skinny-straight” phenotype. Subsequent testing showed that these two compounds had an acute nematocidal effect (within 1–12 h) on adult males and females of H. contortus. Ultrastructural analysis of adult worms treated with compound 4 revealed significant damage to subcuticular musculature and associated tissues and cellular organelles including mitochondria. In conclusion, the present study has discovered two algal compounds possessing acute anthelmintic effects and with potential for hit-to-lead progression. Future work should focus on undertaking a structure-activity relationship study and on elucidating the mode(s) of action of optimised compounds.

Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents

Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.

ANTICANCER AND FREE RADICAL SCAVENGING POTENTIAL OF THE MARINE ALGICOLOUS ENDOPHYTIC FUNGUS CLADOSPORIUM UREDINICOLA

Objective: The objective was to study the antioxidant and anticancer potential of the endophytic fungus Cladosporium uredinicola, isolated from the marine brown alga Dictyota dichotoma. Methods: Anticancer effect of the endophytic fungal extract was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay using MDA-MB-231 human mammary adenocarcinoma cells as in vitro cancer models. 3T3-L1 pancreatic adipocytes were used as in vitro models for the evaluation of cytotoxic activity against normal cells using MTT assay. Free radical scavenging activity was assessed by 2, 2-diphenyl-1- picrylhydrazyl (DPPH) assay. Results: The ethyl acetate extract of the endophytic fungus showed potent cytotoxic activity against MDA-MB-231 human breast adenocarcinoma cell lines with an inhibitory concentration (IC50) value of 373 μg/ml and a very mild cytotoxic effect on 3T3-L1 Cells with an IC50 value of 2403 μg/ml. DPPH free radical scavenging assay of the extract showed an IC50 value of 359 μg/ml indicating its potential free radical scavenging activity. Conclusion: The results indicated that the endophytic fungus C. uredinicola, isolated from the marine brown alga D. dichotoma, acts as a potential source for anticancer and antioxidant metabolites. Moreover, these anticancer metabolites were observed to be less toxic to the normal cells, which make them prospective therapeutic agents.

Inhibitory Effects of the Lipophilic Extracts and An Isolated Meroditerpene of Brown Alga in Pasture Weeds in the Eastern Amazon Region

ABSTRACT: Two lipophilic extracts and atomaric acid (1), an isolated natural product, were obtained from the marine brown alga Stypopodium zonale (Dictyotaceae) to identify and characterize their potential inhibitory effects on the seed germination, radicle elongation, and hypocotyl development of the weeds Mimosa pudica and Senna obtusifolia. The extracts were prepared with hexane and dichloromethane, and atomaric acid (1) was isolated from hexane extract by way of conventional chromatographic methods. During a 15 days period, germination bioassays were performed at 25 oC with a 12 h photoperiod, whereas radicle elongation and hypocotyl development were assayed at 25 oC with a 24 h photoperiod. After, Petri dishes 9.0 cm in diameter were coated with qualitative filter paper, 25 seeds were placed in a germination chamber, while six pregerminated seeds were placed in the Petri dish for 2-3 days. After 10 days, radicle and hypocotyl extension were measured; and the inhibitory potential of the extracts was assessed at 10 ppm and that of the atomaric acid at 5, 10, 15, and 20 ppm. In both M. pudica and S. obtusifolia, dichloromethane extract achieved the greatest rates of inhibition during seed germination (34% and 22%, respectively), radical germination (38% and 30%, respectively), and hypocotyl development (29% and 22%, respectively). At a concentration of 20 ppm, atomaric acid (1) also demonstrated reduced inhibitory potential, with mean values of 58.67% for M. pudica and 48.67% for S. obtusifolia.

Structural Revision of Wentiquinone C and Related Congeners from Anthraquinones to Xanthones Using Chemical Derivatization and NMR Analysis

Wentiquinone C, which was previously isolated from the marine brown alga-derived endophytic fungus Aspergillus wentii EN-48, was found to be a potent antioxidant against α,α-diphenyl-picrylhydrazyl (DPPH) radical. The structure of wentiquinone C was originally assigned as an anthraquinone derivative (1,10-dihydroxy-3-(hydroxymethyl)-8-methoxydibenzo [b,e]oxepine-6,11-dione, 1) by 1D and 2D NMR experiments. However, the minor differences of the chemical shifts between xanthones and anthraquinones were queried, leading to the structure of 1 to be revised as a xanthone analog (8-hydroxy-6-(hydroxymethyl)-3-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, 2) on the basis of a methylation and subsequent NMR measurements, and was confirmed by X-ray crystallographic analysis. The method established in this paper could be applied to the structural re-examination or revision for some of the reported seco-anthraquinone derivatives.

Halogenated and Nonhalogenated Metabolites from the Marine-Alga-Endophytic Fungus Trichoderma asperellum cf44-2

One new bisabolane sesquiterpene, bisabolan-1,10,11-triol (1), one new norbisabolane sesquiterpene, 12-nor-11-acetoxybisabolen-3,6,7-triol (2), two new naturally occurring monoterpenes, (7S)- and (7R)-1-hydroxy-3-p-menthen-9-oic acids (3 and 4), one new naturally occurring trichodenone, dechlorotrichodenone C (5), one new chlorine-containing trichodenone, 3-hydroxytrichodenone C (6), one new diketopiperazine, methylcordysinin A (7), and one new naturally occurring oxazole derivative, 4-oxazolepropanoic acid (8), were isolated from the culture of a marine brown alga-endophytic strain (cf44-2) of Trichoderma asperellum. Their structures and relative configurations were determined by extensive 1D/2D NMR and mass spectrometric data, and the absolute configurations of 3–6 were assigned by analysis of the ECD spectra aided by quantum chemical computations. Compounds 1, 2, 5, and 6 showed growth inhibition of some marine phytoplankton species and pathogenic bacteria.