title: 3,5-Bis(3-alkylaminomethyl-4-hydroxybenzylidene)-4-piperidones: A Novel Class of Potent Tumor-Selective Cytotoxins.
abstract: Novel 4-piperidone derivatives 2a-f are disclosed as potent cytotoxins. Many of these compounds are more potent than the reference drug melphalan. The compounds in series 2, 4-7 display selective toxicities toward various neoplasms compared to some normal cells. 2a is one of the promising lead molecules that display >11-fold higher growth inhibiting potency than 5-fluorouracil against human colon cancer cells. 2a induces apoptosis, DNA fragmentation, and cleavage of poly ADP-ribose polymerase.
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan S7H 5C9, Canada.
authors.forename: Subhas S
authors.initials: SS
authors.lastname: Karki
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan S7H 5C9, Canada.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: Department of Diagnostic and Therapeutic Sciences, Division of Pharmacology, Meikai University School of Dentistry , 1-1 Keyakidai, Sakado, Saitama 350-0238, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.affiliation: Department of Diagnostic and Therapeutic Sciences, Division of Pharmacology, Meikai University School of Dentistry , 1-1 Keyakidai, Sakado, Saitama 350-0238, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.affiliation: Department of Diagnostic and Therapeutic Sciences, Division of Pharmacology, Meikai University School of Dentistry , 1-1 Keyakidai, Sakado, Saitama 350-0238, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Matsuyama University , 4-2 Bunkyo-Chu, Matsuyama, Ehime 790-8578, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven , B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven , B-3000 Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Department of Finance, Nanyang Technological University , Singapore 639798, Singapore.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Dimmock
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan S7H 5C9, Canada.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001597:Benzylidene Compounds; D003603:Cytotoxins; D010881:Piperidones; D011065:Poly(ADP-ribose) Polymerases; D008558:Melphalan; D005472:Fluorouracil