Thiazoline Peptides and a Tris-Phenethyl Urea from Didemnum molle with Anti-HIV Activity

As part of our screening for anti-HIV agents from marine invertebrates, the MeOH extract of Didemnum molle was tested and showed moderate in vitro anti-HIV activity. Bioassay-guided fractionation of a large-scale extract allowed the identification of two new cyclopeptides, mollamides E and F (1 and 2), and one new tris-phenethyl urea, molleurea A (3). The absolute configurations were established using the advanced Marfey’s method. The three compounds were evaluated for anti-HIV activity in both an HIV integrase inhibition assay and a cytoprotective cell-based assay. Compound 2 was active in both assays with IC₅₀ values of 39 and 78 μM, respectively. Compound 3 was active only in the cytoprotective cell-based assay, with an IC₅₀ value of 60 μM.