PTP1B inhibitory and cytotoxic C-24 epimers of Δ28-24-hydroxy stigmastane-type steroids from the brown alga Dictyopteris undulata Holmes

Abstract

Ten stigmastane-type steroids bearing unusual Δ²⁸-24-hydroxy side chains, dictyopterisins A-J, including three pairs of C-24 epimers, dictyopterisins B/C, F/G, 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 ¹H 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 μM, respectively, comparable to the positive control oleanolic acid (IC₅₀, 2.78 μM). 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 μM) and A-549 (IC₅₀ from 1.35 to 2.85 μM).

Keywords: Cytotoxicity; Dictyopteris; Dictyopteris undulata; Dictyopterisins A–J; Dictyotaceae; Modified Mosher's method; PTP1B inhibitory activity; Stigmastane-type steroids; X-ray diffraction; Δ(28)-24-Hydroxy side chain.