Phosphoryl substituted 3,5-bis(arylidene)-4-piperidones posessing high antitumor activity

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Phosphorus, Sulfur, and Silicon
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Phosphoryl Substituted 3,5-
Bis(Arylidene)-4-Piperidones
Posessing High Antitumor
Activity
I. L. Odinets a , M. V. Makarov a , O. I. Artyushin a ,
E. Yu. Rybalkina b , K. A. Lyssenko a , T. V. Timofeeva
c & M. Yu. Antipin a
a A.N.Nesmeyanov Institute of Organoelement
Compounds RAS, Moscow, Russia
b Institute of Carcinogenesis, Blokhin Cancer
Research Center, RAMS, Moscow, Russia
c New Mexico Highlands University, Las Vegas, NM,
USA
Available online: 20 Jun 2008
To cite this article: I. L. Odinets, M. V. Makarov, O. I. Artyushin, E. Yu. Rybalkina,
K. A. Lyssenko, T. V. Timofeeva & M. Yu. Antipin (2008): Phosphoryl Substituted 3,5-
Bis(Arylidene)-4-Piperidones Posessing High Antitumor Activity, Phosphorus, Sulfur, and
Silicon and the Related Elements, 183:2-3, 619-620
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Phosphorus, Sulfur, and Silicon, 183:619–620, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701793246
Phosphoryl Substituted 3,5-Bis(Arylidene)-4-Piperidones
Posessing High Antitumor Activity
I. L. Odinets,1 M. V. Makarov,1 O. I. Artyushin,1
E. Yu. Rybalkina,2 K. A. Lyssenko,1 T. V. Timofeeva,3
and M. Yu. Antipin1
1A.N.Nesmeyanov Institute of Organoelement Compounds RAS,
Moscow, Russia
2Institute of Carcinogenesis, Blokhin Cancer Research Center, RAMS,
Moscow, Russia
3New Mexico Highlands University, Las Vegas, NM, USA
Keywords N-(phosphoryl)-3,5-bis(arylidene)-4-piperidones; N-(phosphorylalkyl)-3,5-
bis(arylidene)-4-piperidones; alkylation; phosphorylation; cytotoxity
3,5-Bis(arylidene)-4-piperidones and related compounds 1 possess anti-
cancer and antioxidant activity (Scheme 1).1,2 Some of these compounds
are also fluorescent, which makes possible to use them as dyes for trac-
ing their cellular pathways during chemotherapy and as agents for
photodynamic therapy.3 The important way to regulate the bioavail-
ability and drug delivery of these compounds to target organs is an
introduction of different substitutes R1 to the N-atom of a piperidone
moiety. Phosphorus-containing groups are prospective as such modi-
fiers and may contribute to the biological activity. Therefore, we inves-
tigated synthetic approaches to phosphorylated arylidenepiperidones
and “structure-activity-fluorescence properties” relationship in this
series.
Direct phosphorylation of NH-precursor 2 by phosphorus(IV) acid
chlorides afforded N-phosphorylated compounds 3. Derivatives 4 with
elongated alkylene-phosphoryl linker could be synthesized only by con-
densation of aldehydes with phosphorylated N-alkylpiperidones as
We are thankful for our financial support from the Russian Basic Research Foundation
(05-03-32692).
Address correspondence to I. L. Odinets, A. N. Nesmeyanov Institute of Orga-
noelement Compounds RAS, Vavilova Str. 28, Moscow, 11991 Russia, E-mail:
odinets@ineos.ac.ru
619

620
I. L. Odinets et al.
SCHEME 1
alkylation of the NH-precursor 2 with alkyl halides surprisingly re-
sulted in quaternary salts 5 as the only reaction products (Scheme 2).
SCHEME 2
Compounds 3–5 demonstrate high antitumor activity against a num-
ber of human cancer cell lines with IC50 values in the range of 0.3–
50·10−6 M including resistant lung carcinoma cell line A549 (com-
pounds 5).
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