Probing the bioactive constituents from chemotypes of the sponge Psammocinia aff. bulbosa.

Since the report of (+)-psymberin (2) in 2004, many synthetic groups have pursued the synthesis of this compound, and our group has further collected Psammocinia aff. bulbosa to successfully isolate more 2. With more (+)-psymberin (2) in hand, additional clonogenic studies, a therapeutic efficacy assessment, and the hollow fiber assay have been completed. The inconsistent production of (+)-psymberin (2) and the classification of six Psammocinia species are further discussed herein. The most recent of these six collections resulted in the isolation of a new brominated cyclic peptide, (-)-psymbamide A (4), which is the first report of a Psammocinia-derived compound in this peptide class. The planar structure was solved via dereplication with Marinlit, HRESIMS, and 1D and 2D NMR techniques, and the absolute configuration determined using Marfey's method.

Inhibition of macromolecular synthesis by cryptophycin-52.

Cryptophycin (CP)-52, a synthetic analog of CP-1, possesses potent and selective antiproliferative activity against human solid tumors both and. Based on an algorithm developed in this laboratory using HCT-116 human colon adenocarcinoma cells, CP-52 exhibited a time- and concentration-dependent antiproliferative effect in the clonogenic assay. Inhibition of both DNA and RNA synthesis was observed in the absence of any effect on protein synthesis following a 24-h exposure to CP-52, at a time when proliferating cells were arrested in the G2/M phase of the cell cycle. In summary, we interpret these data to indicate that the selective inhibition of DNA synthesis may be a major causative factor responsible for the antiproliferative activity of CP-52 and subsequent G2/M arrest.