Shermilamine

Dehydrokuanoniamine B (127) and shermilamine C (128) were isolated from a Cystodytes sp. from Fiji. Their structures were determined by analysis of spectroscopic data. These compounds displayed dose-dependent inhibition of proliferation in human colon tumour cells in vitro [142]. Shermilamines D (129) and E (130) were... 

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

The shermilamines constitute a group of alkaloids characterized by a thiazinone ring attached to the pyridoacridine ring system. Shermilamine A (36) was the first known compound of this series and was isolated by Scheuer et al. from the tunicate Trididemnum sp. [38]. The complete... 

Shermilamines B (37) and C (38) (and also diplamine 46) showed dose-dependent inhibition of proliferation in HCT cells in vitro and inhibited the topoisomerase (TOPO) II-mediated decatenation of kinetoplast DNA (kDNA) in a dose-dependent manner [41]. These results suggest a possible cytotoxicity mechanism for these compounds. Furthermore, shermilamine B also displayed cytotoxicity against KB cells [43] and was reported as a potent regulator of cellular growth and differentiation, affecting cAMP-mediated processes [44]. 

Thiazole-containing pyridoacridines are a group of fused ring alkaloids having a pyrido[4,3,2-w, ]thiazolo[3,2-6]acridinium skeleton related to shermilamines, varamines and diplamine, which were discussed in the sulfide section [37]. The pyridoacridines have a characteristic UV absorption pattern [A.max(MeOH) 245, 307, and 361 nm], which is highly sensitive to the pH of the medium. 

An examination of the composition of polyaromatic alkaloids of the mollusk Chelynotus semperi and an unidentified tunicate, both collected from Mante channel, Pohnpei, resulted in the identification of shermilamine B [129] and kuanoniamines A-D [130-133] (105). Shermilamine was originally found as a metabolite of a tunicate of the genus TruUdanmon (106). 

Tunicates are the only marine invertebrates in which alkaloid biosynthesis has been extensively investigated (189). In addition to the eudistomins, described below, the tripeptide tunichromes have been investigated, by Nakanishi and coworkers at Columbia University, in the solitary tunicate Ascidia nigra (191) and shermilamine, a benzo-3,6-phenanthroline alkaloid, has been studied in Cystodytes dellechiajei, by Steffan and coworkers at the University of Munich (192). The origin of the (3-carboline ring system of the eudistomins has been studied, by Baker s group at Florida Tech, in Eudistoma olivaceum (193, 194). 

Shermilamines A and B were isolated from a purple Trididemnum sp. [146,147], while shermilamine C was reported from a purple fleshy Cystodytes sp. from Fiji [132]. Both shermilamines A and B were reported in a paper which described metabolites from Amphicarpa meridiana and Leptoclinides sp. [145], while shermilamine B was also reported under the name debromoshermilamine from a Red Sea Eudistoma sp, [135]. Biosynthetic studies on shermilamine B have been reported [150]. The... 

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