Nine amino derivatives, compounds 3-11, of avarone were synthesized. Their antibacterial and cytotoxic activities are evaluated, and the results of a prescreen for antitumor effects are reported. Recent studies have revealed that avarol [1] and avarone [2], previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida) (1,2), show a wide variety of biological activities. Both compounds are potent antileukemic agents, in vitro and in vivo (3,4). They were determined to be neither direct mutagens nor premutagens, and they displayed antimutagenic activity (5). Both avarol and avarone inhibit replication of the etiological agent of aquired immune deficiency syndrome (AIDS) (6). These interesting properties and the previous finding that 3' methylamino [5] and 4'-methylamino [6] derivatives of avarone, from D. avara (7), also show interesting biological properties, prompted us to prepare other amino derivatives of avarone and evaluate their antibacterial and antitumor activity. We wish to describe herein the synthesis of nine amino derivatives from avarone by using Me3SiN3, methylamine, ethylamine, alanine, 6-aminopurine (adenine), and glucosamine to obtain a wide series of amino derivatives of avarone, with different polarities. Brine shrimp lethality (8) was used as an indicator of cytotoxicity. This assay was demonstrated to be in excellent agreement with L5178y (mouse lymphoma cells) and L1210 (leukemia cells) assays, using avarol [1] and avarone [2] (9). A prescreen for antitumor activity utilized the potato disc assay, by which the inhibition of crown gall tumors on potato discs inoculated with Agrobacterium tumefaciens was determined (10). Amino derivatives were generally obtained by slowly adding the amine hydrochloride, dissolved in basic solution, to a dilute solution of avarone [2], obtained by Ag2O oxidation of avarol [1], in EtOH or EtOH-H2O (1:1). Using either trimethylsilyl azide or ethylamine, two isomers were obtained with substitution at 3' (3,7) and 4' (4,8) of the benzoquinone ring, as previously described (7) for methylamine derivatives (5,6). Using alanine and glucosamine, only one derivative was obtained, with substitution at 4' (9 and 10, respectively). The position of the substituent was determined by the analysis of 1H-nmr spectra. Signals of protons in the benzoquinone ring are doublets in 3'-substituted compounds and singlets in 4' substituted compounds. Finally, when 6-aminopurine was used, the addition of two adenine nitrogens takes place so that a pyrazine ring is formed. The 1H-nmr spectra, showing in the sp2 region two protons of purine (δ 8.05 and 7.84), one vinylic proton (δ 5.08) due to sesquiterpenoid moiety, and one proton singlet (δ 6.48) attributable to the original benzoquinone ring, suggest 3',4' substitution. All derivatives were tested in antibacterial, brine shrimp, and potato disc assays; the results are reported in Table 1. 4'-Methylamino and 4'-ethylamino derivatives were the most cytotoxic of compounds tested, with an activity comparable to that of avarol, previously reported (9).