Lissoclins

Because of the mild and essentially neutral reaction conditions, Burgess reagent was applied for the construction of the oxazoline intermediates 60 required by Pattendon and co-workers " " for their syntheses of thiangazole 61 and lissoclin-... 

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. 

Table 4.9 Inhibition of CXCBl, CXCR2, and PKCot with Frondosins A and C, and Lissoclin Disulfoxide...

One of the invertebrates collected during the 1994 SIO-RU-SKB collaborative marine invertebrate collection from the Aliwal Shoal off southern Kwazulu-Natal, South Africa was the ascidian Lissoclinum sp.. Bioassay guided fractionation of a methanol extract of this ascidian yielded a novel interleukin-8 inhibitor, lissoclin disulfoxide (88) [84], Interleukin-8 (IL-8), a promoter of neutrophil aggregation and activation, is implicated in a wide range of inflammatory disorders e.g. psoriasis and rheumatoid arthritis [85]. In addition to its potent inhibition of both IL-8 Roc and IL-8 R(3 (IC50 = 0.6 and 0.82 pM respectively) 88 also exhibited activity against the protein kinase C enzyme (IC50 = 1.54 pM) [84]. 

A detailed assessment of the antileukemic properties of norsegoline has been published [144], but no activity data has been reported for lissoclins A andB [14]. 

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