Calmodulin antagonist activity

Marine tunicates are a rich source of intriguing structures and interesting biological activities. Eudistomidin A (1) from the Okinawan tunicate Eudistoma glaucus possesses powerful calmodulin antagonistic activity (IC5o 3 x 10 M). Eudistomidins B-D (2-4) show potent cytotoxicity... 

Eudistomidin A (167) was isolated from an Okinawan tunicate (Eudis-toma glaucus) and exhibited strong calmodulin-antagonistic activity (133). Compound 167 was the first calmodulin antagonist of marine origin and is about 15 times more potent than W-7, a well-known calmodulin antagonist. Eudistomidins B, C, and D (168-170) were obtained from the same... 

A number of metabolites which appear to be derived from Tyrosine, Dopa, or Topa residues and to have similar biogenetic origins to the tunichromes have been reported. Rigidin (48), isolated from the Okinawan marine tunicate Eudistoma c.f. rigida exhibited calmodulin antagonistic activity with an IC50 of 5 x lO M against calmodulin-activated brain phosphodiesterase [42]. Some other pyrrolo[2,3d]pyrimidine-2,4-diones which have been synthesised have shown weak affinity for the benzodiazepine receptor. 

The pyrrolo[2,3-J]pyrimidine skeleton is often encountered in important pharmacologically active substances, and more recently it has been observed in a class of marine natural products known as rigidins. These alkaloids have been obtained from tunicates obtained near Okinawa and New Guinea and they have been shown to exhibit very significant calmodulin antagonist activities. Gupton s... 

Ishibasi M, Ohizumi T, Sasaki H, Nakamura H, Hirata Y, Kobayashi J. Pseudodistomins A and B, novel antineoplastic piperidine alkaloids with calmodulin antagonistic activity from the okinawan tunicate Pseudodistoma kanoko. J. Org. Chem. 1987 52(3) 450 53. 

Kobayashi, J., Cheng, J.-F., Kikuchi, Y, Ishibashi, M., Yamamura, S., Ohizumi, Y, Ohta, T., and Nozoe, S. (1990b) Rigidin, a novel alkaloid with calmodulin antagonistic activity from the Okinawan marine tunicate Eudistoma cf. rigida. Tetrahedron Lett., 31,4617—4620. 

Kobayashi, J., Sato, M., Murayama, T, Ishibashi, M., Walchi, M.R, Kanai, M., Shoji, J., and Ohizurru, Y. (1991d) Konbamide, a novel peptide with calmodulin antagonistic activity from the Okinawan marine sponge Theonella sp./. Chem. Soc. Chem. Common., 1050-1053. 

Lam HY (1984) Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiesterase. Biochem Biophys Res Commun 118 27-32... 

While all of these events are interconnected, the two most critical are neuronal rapid influx of Ca2+ and activation of nNOS, both which trigger all downstream events. Therefore, directly blocking the toxic effects of glutamate /NO, can be achieved through many means, including selective nNOS inhibitors, Ca2+ channel blockers [NMDA, Kainate/AMPA] [ryanodine-sensitive, IP3], calmodulin antagonists, Ca2+... 

RS-20 <10> (<10> calmodulin antagonist, prevents the Ca /calmodulin-mediated activation [24]) [24]... 

Progress has been made on purifying the components of PSI1, particularly for cyanobacteria and spinach chloroplasts. The presence of Ca2+ in the cell-breaking system results in enhanced activity on reconstitution, and it may well be that one of the proteins found is a calcium-binding protein, as supported by the inhibitory effect of the calmodulin antagonist chlorpromazine on activity.377... 

Selegiline inhibits the activity of monoamine B, enhances the release of dopamine, blocks the uptake of dopamine, is a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. 

---