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

Authors
  • Brandão, Pedro1
  • Moreira, Joana1, 2
  • Almeida, Joana3
  • Nazareth, Nair3
  • Sampaio-Dias, Ivo E4
  • Vasconcelos, Vitor2, 5
  • Martins, Rosário2, 6
  • Leão, Pedro2
  • Pinto, Madalena1, 2
  • Saraíva, Lucília3
  • Cidade, Honorina1, 2
  • 1 Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal. , (Portugal)
  • 2 CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal. , (Portugal)
  • 3 LAQV/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. , (Portugal)
  • 4 LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal. , (Portugal)
  • 5 Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, Portugal. , (Portugal)
  • 6 Health and Environment Research Centre, School of Health, Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal. , (Portugal)
Type
Published Article
Journal
Molecules
Publisher
MDPI AG
Publication Date
Mar 30, 2020
Volume
25
Issue
7
Identifiers
DOI: 10.3390/molecules25071578
PMID: 32235535
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium 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 (10), as well as its structurally-related quinone (9), 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 (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) 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 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.

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