3,5-Bis(3-alkylaminomethyl-4-hydroxybenzylidene)-4-piperidones: A Novel Class of Potent Tumor-Selective Cytotoxins

Autor:	Umashankar Das, Subhas S. Karki, Shoko Iwamoto, Masami Kawase, Hiroshi Sakagami, Naoki Umemura, Jan Balzarini, Erik De Clercq, Jonathan R. Dimmock, Stephen G. Dimmock
Rok vydání:	2016
Předmět:	0301 basic medicine Antimetabolites Antineoplastic Stereochemistry Poly ADP ribose polymerase Antineoplastic Agents Apoptosis DNA Fragmentation Bioinformatics Benzylidene Compounds Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Drug Discovery Animals Humans Structure–activity relationship Cytotoxicity Antineoplastic Agents Alkylating Melphalan Piperidones Polymerase Cell Proliferation biology Cytotoxins Cell growth 3. Good health 030104 developmental biology chemistry 030220 oncology & carcinogenesis Benzylidene compounds biology.protein Molecular Medicine DNA fragmentation Fluorouracil Drug Screening Assays Antitumor Poly(ADP-ribose) Polymerases
Zdroj:	Journal of Medicinal Chemistry. 59:763-769
ISSN:	1520-4804 0022-2623
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::405845884f568aa889b924c26230c062 https://doi.org/10.1021/acs.jmedchem.5b01706 Zobrazit plný text záznamu