Varamine

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. 

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. 

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. 

As well as their cytotoxicity, varamines A and B were also reported to exhibit potent antifungal activity [136], while the cystodytin A/B mixture and cystodytin C were 36 times and 13 times repectively more powerful than caffeine in calcium-releasing activity in sarcoplasmic reticulum [130]. 

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