PTP1B inhibitory and cytotoxic C-24 epimers of Delta(28)-24-hydroxy stigmastane-type steroids from the brown alga Dictyopteris undulata Holmes

Ten stigmastane-type steroids bearing unusual Delta(28)-24-hydroxy side chains, dictyopterisins A-J, including three pairs of C-24 epimers, dictyopterisins B/C, FIG, and I/J, were isolated from the brown alga Dictyopteris undulata Holmes, together with two previously reported analogues, (24S)- and (24R)-saringosterol. Their structures were elucidated on the basis of extensive spectroscopic analysis, with their absolute configurations at the stereogenic center C-24 of the side chain being assigned by a direct comparison of H-1 NMR data with those of related known compounds. The absolute configurations of the steroidal nuclei of dictyopterisins A, B, and H were determined using the modified Mosher's method. The mixture of dictyopterisins D and E and dictyopterisin I exhibited promising PTP1B inhibitory activities with IC50 values of 1.88 and 3.47 mu M, respectively, comparable to the positive control oleanolic acid (IC50, 2.78 mu M). In addition, the mixture of dictyopterisins D and E and dictyopterisins F-J displayed significant cytotoxicities against the human cancer cell lines HL-60 (IC50 from 1.02 to 2.70 mu M) and A-549 (IC50 from 135 to 2.85 mu M). (C) 2017 Elsevier Ltd. All rights reserved.