title: 1-[3-(2-Hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-piperidones: A novel cluster of P-glycoprotein dependent multidrug resistance modulators.
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.
authors.affiliation: 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.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
authors.forename: Hari N
authors.initials: HN
authors.lastname: Pati
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Szeged, Szeged H-6720, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Baráth
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Szeged, Szeged H-6720, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Csonka
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Szeged, Szeged H-6720, Hungary.
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.affiliation: 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.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: C526290:3,5-bis(benzylidene)-4-piperidone; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010881:Piperidones
keywords: 3,5-Bis(benzylidene)-4-piperidones; MDR revertants; P-glycoprotein; Selective cytotoxicity; Structure–activity relationships