Two new cyclopeptides, perthamides E and F were isolated from the polar extracts of the sponge Theonella swinhoei. The new structures, featuring an unprecedented beta-amino acid unit (AHMOA), were determined by interpretation of NMR and MS data. The absolute configuration of the AHMOA residue was proposed on the basis of quantum chemical calculation of NMR chemical shifts. Perthamides were proved to inhibit TNF-alpha and IL-8 release in primary human keratinocytes cells and therefore could represent potentially leads for the treatment of psoriasis.