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

  • Molecules. 2020 Mar 30;25(7):1578. doi: 10.3390/molecules25071578.
Pedro Brandão  1 ,  Joana Moreira  1  2 ,  Joana Almeida  3 ,  Nair Nazareth  3 ,  Ivo E Sampaio-Dias  4 ,  Vitor Vasconcelos  2  5 ,  Rosário Martins  2  6 ,  Pedro Leão  2 ,  Madalena Pinto  1  2 ,  Lucília Saraíva  3 ,  Honorina Cidade  1  2
Affiliations
  • 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.
  • 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.
  • 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.
  • 4. LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
  • 5. Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007 Porto, 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.
PMID: 32235535 DOI: 10.3390/molecules25071578
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.

Keywords
antitumor activity; hierridin B; hydroquinones; quinones.
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