Publication:


abstract

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.

Related Articles
Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis.
Anticancer Res. 2011
Modulation of multidrug efflux pump activity by new hydantoin derivatives on colon adenocarcinoma cells without inducing apoptosis.
Spengler G, Handzlik J, Ocsovszki I, Viveiros M, Kiec-Kononowicz K, Molnar J, Amaral L. Anticancer Res. 2011 Oct; 31(10):3285-8.
Biological activity of twenty-three hydantoin derivatives on intrinsic efflux pump system of Salmonella enterica serovar Enteritidis NCTC 13349.
In Vivo. 2011
Biological activity of twenty-three hydantoin derivatives on intrinsic efflux pump system of Salmonella enterica serovar Enteritidis NCTC 13349.
Machado L, Spengler G, Evaristo M, Handzlik J, Molnár J, Viveiros M, Kiec-Kononowicz K, Amaral L. In Vivo. 2011 Sep-Oct; 25(5):769-72.
The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of Staphylococcus aureus.
In Vivo. 2012
The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of Staphylococcus aureus.
Dymek A, Armada A, Handzlik J, Viveiros M, Spengler G, Molnar J, Kieć-Kononowicz K, Amaral L. In Vivo. 2012 Mar-Apr; 26(2):223-9.
Review N,N-bis(cyclohexanol)amine aryl esters: the discovery of a new class of highly potent inhibitors of transporter-dependent multidrug resistance (MDR).
Curr Top Med Chem. 2010
Review N,N-bis(cyclohexanol)amine aryl esters: the discovery of a new class of highly potent inhibitors of transporter-dependent multidrug resistance (MDR).
Teodori E, Dei S, Martelli C, Scapecchi S. Curr Top Med Chem. 2010; 10(17):1715-31.
Review Molecular mechanisms of multidrug resistance in cancer chemotherapy.
Pathol Res Pract. 1996
Review Molecular mechanisms of multidrug resistance in cancer chemotherapy.
Nooter K, Stoter G. Pathol Res Pract. 1996 Jul; 192(7):768-80.