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Home / Publicações / Activity of fourteen new hydantoin compounds on the human ABCB1 efflux pump.

Activity of fourteen new hydantoin compounds on the human ABCB1 efflux pump.

  • Autores: Amaral L, Armada A, Dymek A, Handzlik J, Kiec-Kononowicz K, Martins A, Molnar J, Spengler G
  • Journal: In vivo
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Activity+of+Fourteen+New+Hydantoin+Compounds+on+the+Human+ABCB1+Efflux+Pump

BACKGROUND:
Multidrug resistance (MDR) is one of the major concerns in the treatment of cancer and one of the major causes of therapy failure. The overexpression of an ABC transporter, the ABCB1, is often associated with MDR in cancer. Previously it was observed that hydantoin compounds can modulate the activity of the ABCB1 pump.

MATERIALS AND METHODS:
Fourteen hydantoin derivatives were synthesized and studied for their capacity to increase accumulation of ethidium bromide (EB) by mouse lymphoma cancer cells that were transfected with the human ABCB1 gene and overexpress the human ABCB1 pump.

RESULTS:
It was observed that the accumulation of EB by the cells in the presence of four of the newly synthesized hydantoins was strongly increased. Similar but milder effects were also observed for the other seven hydantoins; the remaining three had no activity.

CONCLUSION:
The 14 hydantoin compounds studied belong to three different structural groups. Structure-activity relationships were studied and important molecular substituents that were possibly responsible for increased the activity of the molecules were identified. This important information may lead to the continuation of our work and to the future synthesis of more active compounds.

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GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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