title: Niacin esters of chalcones with tumor-selective properties.
abstract: Novel series of niacin esters of chalcones 2, 4 and 6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4(+ )T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure-activity relationship (QSAR) studies of the biodata in series 4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor-selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series 2, 4 and 6 have positive characteristics which warrant further studies.
authors.affiliation: a Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon , Canada .
authors.forename: Atulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: a Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon , Canada .
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: a Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon , Canada .
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Roayapalley
authors.affiliation: b Division of Pharmacology , Meikai University School of Dentistry , Sakado , Saitama , Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.affiliation: c Faculty of Pharmaceutical Sciences , Matsuyama University , Matsuyama , Japan , and.
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.affiliation: d Rega Institute of Medical Research, KU Leuven , Leuven , Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: d Rega Institute of Medical Research, KU Leuven , Leuven , Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: a Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon , Canada .
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D006801:Humans; D009525:Niacin / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D004952:Esters; D009525:Niacin
keywords: Chalcones; QSAR; cytotoxicity; niacin; tumor-specific toxicity; unsaturated ketones