Diplamines

The methyl sulfide-containing alkaloids, varamines A (123) and B (124) were isolated from L. vareau. Their structures were determined by interpretation of NMR spectral data and by comparison with related alkaloids. The varamines were cytotoxic towards L1210 murine leukaemia cells with IC50 values of 0.03 and 0.05 Xg/mL, respectively [138], The varamines (123-124), lissoclins (110-111) and diplamine (112) all contain a methyl sulfide group linked to a pyridoacridine ring system [22],... 

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. 

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. 

Diplamine Cytotoxic toward L1210 leukemia cells 0.002 g/ml 189... 

The structure of norsegoline (184), which was isolated from a Eudistoma sp. from the Red Sea, was disclosed in two reports [134,135], while varamines A (185) and B (186) were isolated from a Fijian collection of Lissoclimm vareau [136]. Syntheses of cystodytin J [138], other cystodytins [139], diplamine [138,140,141], and norsegoline [142,143] have been reported. 

In 1989, Ireland et al. reported the isolation and structure elucidation of diplamine (399), which is a member of the pyridoacridine type alkaloids 175). 

Diplamine was isolated from a Diplosoma sp. tunicate collected in the Fiji Islands. Flash column chromatography of the extract from the tunicate, using silica gel as support and CHCls/MeOH (90 10) as the eluting solvent, yielded 0.08% of diplamine. 

LissocNnuin alkaloids. Pyrido[2,3,4-k/]acridinone (e.g., diplamine, cf. kuanoniamines) and harman alkaloids from tropical tunicates of the genus Lissocli-... 

Diplamine CaoH NjOaS, Mr 363.43, orange solid, mp. 202-204°C, cytotoxic. 

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