1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance

Umashankar Das, J. Molnár, Zoltán Baráth, Z. Bata-Csörgő, Jonathan R. Dimmock

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The 1-[4-(2-aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 μg/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings.

Original languageEnglish
Pages (from-to)3484-3487
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number12
DOIs
Publication statusPublished - Jun 15 2008

Fingerprint

Multiple Drug Resistance
P-Glycoprotein
Verapamil
Amines
Genes
Structure-Activity Relationship
Lymphoma
3,5-bis(benzylidene)-4-piperidone

Keywords

  • Multidrug resistance
  • N-Aroyl-3,5-bis(benzylidene)-4-piperidones
  • Physicochemical constants
  • Structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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title = "1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance",
abstract = "The 1-[4-(2-aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 μg/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings.",
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author = "Umashankar Das and J. Moln{\'a}r and Zolt{\'a}n Bar{\'a}th and Z. Bata-Cs{\"o}rgő and Dimmock, {Jonathan R.}",
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AU - Das, Umashankar

AU - Molnár, J.

AU - Baráth, Zoltán

AU - Bata-Csörgő, Z.

AU - Dimmock, Jonathan R.

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N2 - The 1-[4-(2-aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 μg/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings.

AB - The 1-[4-(2-aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidin es 5-8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 μg/mL, these compounds possess 11-43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure-activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings.

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KW - Structure-activity relationships

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