Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells

G. Spengler, Miguel Evaristo, Jadwiga Handzlik, Julianna Serly, J. Molnár, Miguel Viveiros, Katarzyna Kieć-Kononowicz, Leonard Amaral

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. Materials and Methods: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. Results: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. Conclusion: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.

Original languageEnglish
Pages (from-to)4867-4872
Number of pages6
JournalAnticancer Research
Volume30
Issue number12
Publication statusPublished - Dec 2010

Fingerprint

Hydantoins
P-Glycoprotein
Rhodamine 123
Lymphoma
Fluorometry
Doxorubicin
Ethidium
Amines
Pharmacology
Neoplasms

Keywords

  • ABCB1
  • Cancer
  • Hydantoin
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spengler, G., Evaristo, M., Handzlik, J., Serly, J., Molnár, J., Viveiros, M., ... Amaral, L. (2010). Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells. Anticancer Research, 30(12), 4867-4872.

Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells. / Spengler, G.; Evaristo, Miguel; Handzlik, Jadwiga; Serly, Julianna; Molnár, J.; Viveiros, Miguel; Kieć-Kononowicz, Katarzyna; Amaral, Leonard.

In: Anticancer Research, Vol. 30, No. 12, 12.2010, p. 4867-4872.

Research output: Contribution to journalArticle

Spengler, G, Evaristo, M, Handzlik, J, Serly, J, Molnár, J, Viveiros, M, Kieć-Kononowicz, K & Amaral, L 2010, 'Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells', Anticancer Research, vol. 30, no. 12, pp. 4867-4872.
Spengler, G. ; Evaristo, Miguel ; Handzlik, Jadwiga ; Serly, Julianna ; Molnár, J. ; Viveiros, Miguel ; Kieć-Kononowicz, Katarzyna ; Amaral, Leonard. / Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells. In: Anticancer Research. 2010 ; Vol. 30, No. 12. pp. 4867-4872.
@article{a74bfdfe2311428ab9fd095b2eb3295f,
title = "Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells",
abstract = "Background: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. Materials and Methods: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. Results: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. Conclusion: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.",
keywords = "ABCB1, Cancer, Hydantoin, Multidrug resistance, P-glycoprotein",
author = "G. Spengler and Miguel Evaristo and Jadwiga Handzlik and Julianna Serly and J. Moln{\'a}r and Miguel Viveiros and Katarzyna Kieć-Kononowicz and Leonard Amaral",
year = "2010",
month = "12",
language = "English",
volume = "30",
pages = "4867--4872",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "12",

}

TY - JOUR

T1 - Biological activity of hydantoin derivatives on P-Glycoprotein (ABCB1) of mouse lymphoma cells

AU - Spengler, G.

AU - Evaristo, Miguel

AU - Handzlik, Jadwiga

AU - Serly, Julianna

AU - Molnár, J.

AU - Viveiros, Miguel

AU - Kieć-Kononowicz, Katarzyna

AU - Amaral, Leonard

PY - 2010/12

Y1 - 2010/12

N2 - Background: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. Materials and Methods: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. Results: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. Conclusion: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.

AB - Background: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. Materials and Methods: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. Results: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. Conclusion: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.

KW - ABCB1

KW - Cancer

KW - Hydantoin

KW - Multidrug resistance

KW - P-glycoprotein

UR - http://www.scopus.com/inward/record.url?scp=78751480306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78751480306&partnerID=8YFLogxK

M3 - Article

C2 - 21187464

AN - SCOPUS:78751480306

VL - 30

SP - 4867

EP - 4872

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 12

ER -