Biologically active compounds from marine organisms.

During the past 30 to 40 years, numerous novel compounds have been isolated from marine organisms and many of these have been reported to have biological activities, some of which are of interest from the point of view of potential drug development. On the other hand, some of the compounds pose potential risks to human health. In this latter category are the paralytic, diarrhetic and amnesic shellfish toxins. From time to time, large concentrations of dinoflagellates occur in the sea, which because of their pigmentation, give the water a rusty-brown to red colouration. Such phenomena are known as ‘red tides’. Some of the dinoflagellate species produce toxins, which concentrate in the flesh of filter feeders, such as shellfish, when they consume the dinoflagellates. In turn, when the shellfish are eaten by humans, severe toxic effects can result. The toxins are referred to as either paralytic or diarrhetic shellfish poisons. The former can prove fatal, but the latter, although producing very unpleasant effects, are not fatal. The most well-known paralytic shellfish toxin is saxitoxin (Fig. 1), although other related compounds have been reported, such as neosaxitoxin, the 11and 11-O-sulphates of saxitoxin and neosaxitoxin, and carbonyl-N-sulphate derivatives of saxitoxin and neosaxitoxin (Faulkner, 1986). These compounds are produced from certain species of Alexandrium and Gymnodinium. Ptychodiscus brevis produces another class of paralytic shellfish toxins known as brevetoxins, the most potent of which is brevetoxin A (Fig.1). Of the diarrhetic shellfish toxins, the best known are the dinophysistoxins, for example dinophysistoxin 1 (Fig. 1), which are produced by Dinophysis species, such as D. fortii (Yasumoto et al., 1985). Other compounds producing diarrhetic shellfish toxicity are the pectenotoxins (Fig. 1) (Lee et al., 1989). Because of the potential health hazards of paralytic and diarrhetic shellfish poisoning, monitoring programmes on shellfish toxicity have been introduced in many countries. For paralytic shellfish poisons, the methods include mouse tests as well as HPLC procedures (Nagashima et al., 1989; Oshima et al., 1989). For diarrhetic shellfish toxins, methods include bioassays, immunoassays and physicochemical methods (Fremy et al., 1999). Whereas both paralytic and diarrhetic shellfish toxins are produced by dinoflagellates, amnesic shellfish poisoning results from the ingestion of shellfish contaminated with diatoms. In 1987, over 100 cases of poisoning, including three fatalities, were recorded for eastern Canada as a result of people eating infected mussels. The toxic compound was shown to be domoic acid (Fig. 1), produced by the diatom Pseudonitzschia pungens forma multiseries. The effects of domoic acid poisoning include gastrointestinal symptoms such as nausea, vomiting, anorexia, gastric bleeding, diarrhoea and abdominal cramps, followed by neurological disorders such as confusion, disorientation, loss of shortterm memory, coma and death (Lundholm et al., 1994). The ingestion of other marine organisms can also lead to serious poisoning. Well known examples include the potent neurotoxin tetrodotoxin, resulting from eating pufferfish, and ciguatoxin, associated with ingestion of tropical fish which have fed on the dinoflagellate, Gambierdiscus toxicus.