Design, cytotoxic and fluorescent properties of novel N-phosphorylalkyl substituted E,E-3,5-bis(arylidene)piperid-4-ones.
A series of E,E-N-phosphorylalkylene-3,5-bis(arylidene)piperid-4-ones 7a-k was prepared via the condensation of aromatic aldehydes with omega-aminophosphonates 5a-c and 6a,b bearing piperidone or a protected piperidone moiety, respectively. The synthetic routes to the starting aminophosphonates 5a-c and 6a,b varied depending on the number of methylene groups in the alkylene chain and comprised the Kabachnik-Fields reaction (n=1), the aza-Michael reaction (n=2) or alkylation of 4-piperidone hydrochloride with diethyl omega-bromoalkylphosphonates under phase transfer catalysis conditions (n=3,4). Phosphoryl substituted 3,5-bis(arylidene)piperid-4-ones 7b,c,e,f,h,i,k bearing both nitro groups and fluorine atoms in the para-position of the arene rings possess cytotoxicity toward human carcinoma cell lines CaOv3, Scov3, PC3 and A549 in the low micromolar range while their analogues having para-dimethylamino groups had IC(50) values greater than 50 microM. In contrast, only Me(2)N-substituted phosphonates 7g,j (n=3 and 4) and the salts of Me(2)N-substituted phosphonic acids 10c,f (n=2 and 3) display fluorescence.
Makarov
Michael V
MV
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova str. 28, 119991 Moscow, Russia.
Rybalkina
Ekaterina Yu
EY
Röschenthaler
Gerd-Volker
GV
Short
Kurt W
KW
Timofeeva
Tatiana V
TV
Odinets
Irina L
IL
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D063065:Organophosphonates; D010881:Piperidones / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D063065:Organophosphonates; D010881:Piperidones