Bromotyrosine derivatives antimicrobial activity

Four minor metabolites, psammaplins B-D (503-505) and presammaplin A (506) were isolated from Psammaplysilla purpurea, in addition to psammaplin A (500). Psammaplin B (503) is a thiocyanate bromotyrosine derivative, while psammaplin C (502) is a sulfanamide. Psammaplin D (505) displayed antimicrobial activity and mild tyrosine kinase inhibition [429]. The psammaplins Ai (507) and A2 (508) and aplysinellins A (509) and B (510) were isolated from Aplysinella rhax from both Pohnpei and Palau. These compounds inhibit famesyl protein transferase and leucine aminopeptidase [430]. Another sample of A. rhax from the Great Barrier Reef, Australia contained psammaplin A 11 -sulfate (511) and bisaprasin ll -sulfate (512), both of which inhibited [3H]-l,3-dipropyl-8-cyclopentylxanthine binding to rat brain adenosine Ai receptors [431]. 

Bromotyrosine-derived metabolites are often encountered in marine sponges of the families Aplysinidae and Pseudocer-atidae, in particular Pseudoceratina (= Psammaplysilla) purpurea. They show a variety of biological activities, which include antimicrobial, enzyme inhibitory, and antifouling activities. Psammaplysin A (47) is antimicrobial, cytotoxic, and antifouling, whereas psammaplin A (48) is an inhibitor of histone deacetylase (2). The marine sponge lanthella basta synthesizes at least 25 bastadins that are linear or cyclic peptides composed of four bromotyrosine residues [bastadin 5 (49)] and show antimicrobial, cytotoxic, and enzyme inhibitory activities as well as interaction with Ca + channels (21). 

Purealidin C (192) was isolated from the Okinawan sponge P. purea, which exhibited cytotoxic, antifungal, and antimicrobial activities ( 4), Tokaradines A (193) and B (194), isolated from Pseudoceratina purpurea, are rare examples of marine bromotyrosine-derived metabolites containing an A-substituted pyridinium group. 

Bromotyrosine derivatives were first isolated in the process of searching for antibiotics from marine sources. The dienone 1, aeroplysinin-1 (14), and aerothionin (68) are the earliest antimicrobial bromotyrosine derivatives (2,14,58). The antibacterial and antifungal activities of the bromotyrosine alkaloids are summarized in Table IV and... 

Both ll-oxo-12-hydroxyaerothionin (73) and 11-hydroxyaerothionin (71) induced 60 and 70% inhibition, respectively, of Mycobacterium tuberculosis growth at 12.5 pg/mL, while 11-oxoaerothionin (72) induced no inhibition at all (253). Single spirocyclohexa-dienylisoxazoline bromotyrosine derivatives, aplysinamisine I (120), aplysinamisine n (124), aplysinamisine III (102), purealidin B (109), araplysillin-I (99), and araplysillin-II (100), showed moderate antimicrobial activity (81,83,84). Some of the oxime type bromotyrosine derivatives showed potent antimicrobial activity. Anomoian A (195), a reduced oxime, exhibited strong antimicrobial activity against Staphylococcus aureus at 10 pg/disk. Bacillus. subtilis at 5 pg/disk, and Candida albicans at 25 pg/disk. 

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