Ted R. Norton

Toxins from cyanophytes belonging to the scytonemataceae

Two highly cytotoxic substances, scytophycins A and B, have been isolated from cultured Scitonema pseudohofmanni. Gross structures are proposed for scytophycins A and B, mostly on the basis of nuclear magnetic resonance spectral studies. The scytophycins are structurally related to tolytoxin, a toxic lipid found in field-collected Tolypothrix conglutinata var. colorata, another blue-green alga belonging to the family Scytonemataceae. At sublethal doses the scytophycins display moderate activity against P-388 lymphocytic leukemia and Lewis lung carcinoma in mice.

Identification of a cytotoxin from Tolypothrix byssoidea as tubercidin

Abstract Tubercidin, a biologically active pyrrolo[2,3-d]pyrimidine nucleoside previously isolated from Streptomyces tubercidicus , has been identified as a major metabolise of the cyanophyte Tolypothrix byssoidea .

Antitumor Activity in Mice of Tentacles of Two Tropical Sea Annelids

Crude extracts of tentacles of two polychaetous annelids completely inhibit growth of Erlich ascites tumor in 60 to 100 percent of treated mice. Dialyzed extracts of one of these annelids, Lanice conchilega, show activity in the retentate after pronase digestion, suggesting that antitumor activity is associated with a nonprotein component of the crude tentacle extract.

Electrical and Mechanical Effects of Anthopleurin-A, a Polypeptide from a Sea Anemone, on Isolated Rabbit Ventricular Muscle Under Conditions of Hypoxia and Glucose-Free Medium

Summary: The effects of anthopleurin-A (AP-A, 1 x 10-H M) on the membrane action potential and contraction of isolated rabbit ventricular muscle were compared with those of ouabain (5 x 10-7 M). Under control conditions. AP-A and ouabain showed submaximal (about 80% of maximal) positive inotropic effects without any toxic manifestations. AP-A caused a marked prolongation of action potential duration (APD) without affecting any other parameters of the action potential, whereas ouabain caused a shortening of APD and a slight decrease in maximum diastolic potential (MDP), overshoot (OS), and upstroke velocity (dV/dtmax) of the action potential. The positive inotropic effect of AP-A was relatively well maintained even under hypoxia or in glucose-free medium. Under these abnormal experimental conditions, AP-A caused a prolongation of APD only at the late stage of repolarization(APDmax), whereas APD at the early stage of repolarization (APD30) was further shortened. Other parameters of action potential and resting tension (RT) were not influenced by AP-A. In contrast, under similar experimental conditions, ouabain caused no apparent positive inotropic action, but resulted in a marked increase in RT (contracture). In addition, after exposure to ouabain, a progressive shortening of APD and marked decreases in MDP. OS, and dV/dtmax were observed. These results indicate that AP-A has pharmacological properties quite different from those of ouabain and suggest possible advantages of this newly developed cardiononic agent over cardiac glycosides when acting on the energy-depleted myocardium.

A possible mechanism of action of a central stimulant substance isolated from the sea anemone Stoichactis enti

Abstract An active fraction causing central stimulation (evidence as fighting episodes) in mice has been isolated from a sea anemone, most probably Stoichactis kenti . It was found to be a basic polypeptide. The ED 50 of the active fraction was 6.4 mg/kg (i.p.) and LD 50 was 12.2 mg/kg (i.p.). The antagonism of the active fraction-induced stimulant activity by phenobarbital sodium, chlorpromazine and methocarbamol suggests that this activity was probably mediated centrally. Reserpine or tetrabenazine, but not α-methyl-p-tyrosine (α-MPT) pretreatment, decreased the ED 50 of the active fraction. D,L-Dopa treatment also decreased the ED 50 of the active fraction and restored the stimulant action after its abolition by combined treatment with α-MPT and reserpine or α-MPT and disulfiram. These results suggest that a central adrenergic mechanism plays a major role in this stimulant action of the active substance; inhibition by β-adrenoceptor antagonists also support this hypothesis. Interactions with cholinergic and anticholinergic drugs also exist which are not incompatible with this hypothesis.

Effects of a central stimulant substance isolated from the sea anemone Stoichactis kenti on brain monoamines of the mouse

An active substance, polypeptide in chemical nature, causing central stimulant activity in mice has been isolated from a sea anemone. Signs of central nervous stimulatory activity produced by this substance included fighting episodes, increased motor activity and clonic convulsions. The active substance produced significant decreases in brain norepinephrine concentration both at the ED50 (6.4 mg/kg) and the maximum effective dose (9.3 mg/kg) during the stimulation period. Brain dopamine concentration was significantly decreased by the active substance at the ED50 dose whereas brain serotonin concentration was not affected. The ED50 dose of the active substance significantly inhibited the re-uptake of norepinephrine during the stimulation period and elevated hormetanephrine levels. These results suggest that the active substance causes central stimulation by releasing active norepinephrine from functional pools and inhibiting its re-uptake, thus making more norepinephrine available at a adrenoceptors. It is probable that brain dopamine plays a minor role in this stimulant action of the active substance.