Norhierridin B, a New Hierridin B-Based Hydroquinone with Improved Antiproliferative Activity.

Hierridin B (), a methylated hydroquinone isolated from the marine picocyanobacterium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (), as well as its structurally-related quinone (), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B () showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B () interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone when compared to and its structurally-related quinone (). Notably, hydroquinone displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.