2. Academic Validation
  3. 1-[3-(2-Hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-piperidones: A novel cluster of P-glycoprotein dependent multidrug resistance modulators

1-[3-(2-Hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-piperidones: A novel cluster of P-glycoprotein dependent multidrug resistance modulators

  • Bioorg Med Chem Lett. 2016 Feb 15;26(4):1319-21. doi: 10.1016/j.bmcl.2016.01.005.
Umashankar Das 1,  Hari N Pati 2,  Zoltan Baráth 3,  Ákos Csonka 3,  Joseph Molnár 3,  Jonathan R Dimmock 4
Affiliations

Affiliations

  • 1 Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. Electronic address: umashankar.das@usask.ca.
  • 2 Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
  • 3 Institute of Medical Microbiology and Immunology, University of Szeged, Szeged H-6720, Hungary.
  • 4 Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. Electronic address: jr.dimmock@usask.ca.
PMID: 26796064 DOI: 10.1016/j.bmcl.2016.01.005
Abstract

A series of 1-[3-(2-hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-piperidones 4a-e display promising P-glycoprotein dependent multidrug resistance (MDR) revertant properties and are significantly more potent than a reference drug verapamil when evaluated against L-5178Y MDR lymphoma cells. These dienones may be referred to as dual agents having both MDR revertant properties and tumour-selective cytotoxicity. In particular, 3,5-bis(4-chlorobenzylidene)-1-[3-(2-hydroxyethylsulfanyl]propanoyl-4-piperidone 4d emerged as a lead molecule for further development based on its MDR revertant properties, cytotoxic potencies and tumour-selective toxicity. The structure-activity relationships reveal important structural requirements for further designing of potent MDR revertants.

Keywords

3,5-Bis(benzylidene)-4-piperidones; MDR revertants; P-glycoprotein; Selective cytotoxicity; Structure–activity relationships.

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