Extracts of samples of a Caribbean tunicate (ascidian, sea squirt) of the family Didemnidae inhibit in vitro at low concentrations the growth of DNA and RNA viruses as well as L1210 leukemic cells. The active compounds isolated from the tunicate, didemnins A, B, and C, are depsipeptides, and didemnin B (a derivative of didemnin A) is the component active at the lowest concentration in inhibiting viral replication in vitro and P388 leukemia in vivo.

Bioactivities of 42 didemnin congeners, either isolated from the marine tunicates Trididemnun solidum and Aplidium albicans or prepared synthetically and semisynthetically, have been compared. The growth inhibition of various murine and human tumor cells and plaque reduction of HSV-1 and VSV grown on cultured mammalian cells were used to assess cytotoxicity and antiviral activity. Biochemical assays for macromolecular synthesis (protein, DNA, and RNA) and enzyme inhibition (dihydrofolate reductase, thymidylate synthase, DNA polymerase, RNA polymerase, and topoisomerases I and II) were also performed to specify the mechanisms of action of each analogue. Immunosuppressive activity of the didemnins was determined using a mixed lymphocyte reaction (MLR) assay. These assays revealed that the native cyclic depsipeptide core is an essential structural requirement for most of the bioactivites of the didemnins, especially for cytotoxicities and antiviral activities. The linear side-chain portion of the peptide can be altered with a gain, in some cases, of bioactivities. In particular, dehydrodidemnin B, tested against several types of tumor cells and in in vivo studies in mice, as well as didemnin M, tested for the mixed lymphocyte reaction and graft vs host reaction in murine systems, showed remarkable gains in their in vitro and in vivo activities compared to didemnin B.

Biologically active extracts of the Caribbean sponge Agelas conifera have yielded, in exhaustive studies, the diacetate salts of seven new bromopyrroles (1,(3)(4)(5)(6)(7)(8), as well as that of the known debromooroidin dimer sceptrin (2). These compounds were found to be antiviral and antibacterial and were active in barnacle settlement and biochemical prophage induction assays. The structures assigned were based on spectroscopic comparisons to sceptrin and two-dimensional NMR data. Synthetic bromopyrroles were used to verify bromine substitution patterns. The oxysceptrins (4,5) are characterized by their aminoimidazolinone group, the ageliferins (6-8) by a unique cyclohexene-based skeleton.