Synthesis and biological evaluation of the 12,12-dimethyl derivative of Aplog-1, an anti-proliferative analog of tumor-promoting aplysiatoxin.

Aplog-1 is a unique analog of tumor-promoting aplysiatoxin that inhibits tumor-promotion by phorbol diesters and proliferation of tumor cells. While the structural features relevant to the biological activities of Aplog-1 remain to be identified, recent studies by us have suggested that local hydrophobicity around the spiroketal moiety of Aplog-1 is a crucial determinant of its anti-proliferative activity. This hypothesis led us to design 12,12-dimethyl-Aplog-1 (3), in which a hydrophobic geminal dimethyl group is installed proximal to the spiroketal moiety to improve biological potency. As expected, 3 was more effective than Aplog-1 in inhibiting cancer cell growth and binding to protein kinase Cδ, a putative receptor responsible for the biological response of Aplog-1. Moreover, an induction test on Epstein-Barr virus early antigen demonstrated 3 to be a better anti-tumor promoter than Aplog-1. These results indicate that 3 is a superior derivative of Aplog-1, and thus a more promising lead for anti-cancer drugs.

The freshwater cyanobacterium Lyngbya aerugineo-coerulea produces compounds toxic to mice and to mammalian and fish cells.

Despite a growing awareness of the presence of cyanobacterial toxins, knowledge about the ability of specific species to produce toxic compounds is still rather limited. It was the overall goal of the current work to investigate if probes derived from the freshwater species Lyngbya aerugineo-coerulea (Kutz.) Gomont, a cyanobacterium frequently found in southern Europe and not previously investigated for the presence of bioactive compounds, were capable of eliciting in vivo and in vitro toxicity. The cyanobacterial extract revealed signs of neuro- as well as hepatotoxicity in mice, although these signs could not be explained by the well-known respective cyanobacterial neuro- and hepatotoxins saxitoxin and microcystin. Cytotoxicity was elicited by the cyanobacterial extract in all mammalian cell lines tested. As well, the rainbow trout liver cell line, RTL-W1, was found to be susceptible to the cytotoxic effects of the extract, although the cytotoxicity was dependent on temperature. In contrast, the cyanobacterial growth medium elicited cytotoxicity independent of temperature, leading to morphological changes indicative of alterations to the cytoskeleton. Overall, the results suggest that Lyngbya aerugineo-coerulea is an important cyanobacterium to be considered for its potential to cause health risks on environmental exposure of it to mammals and fish. Applying a combination of mammalian and piscine cell line bioassays is a unique approach that, combined with chemical analysis, could be used in the future to identify the structure and cellular mechanisms of the as-yet-unknown toxic Lyngbya aerugineo-coerulea metabolites in particular and to screen cyanobacterial extracts for their toxicity in general.

The toxins of Lyngbya majuscula and their human and ecological health effects.

Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles.

Vibrio in stinging seaweed: potential infection.

Toxic strains of the finely filamentous, velvety, dark-olive green to black algal organism, Microcolus Lyngbyaceus, (formerly Lyngbya majuscula Gomont, or "lyngbya") have been recognized as etiologic agent of "stinging seaweed" dermatitis (one of several forms of "swimmer's itch") in Hawaii since the late 1950s as reviewed. Lymphadenopathy, pustular folliculitus, and local infections have been reported in some persons.