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 we...

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Veröffentlicht in:Molecules (Basel, Switzerland) Switzerland), 2020-03, Vol.25 (7), p.1578
Hauptverfasser: Brandão, Pedro, Moreira, Joana, Almeida, Joana, Nazareth, Nair, Sampaio-Dias, Ivo E, Vasconcelos, Vitor, Martins, Rosário, Leão, Pedro, Pinto, Madalena, Saraíva, Lucília, Cidade, Honorina
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Sprache:eng
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Zusammenfassung: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules25071578