Synthesis of 4'-hydroxy-3'-piperidinomethylchalcone derivatives and their cytotoxicity against PC-3 cell lines.
A new series of mono Mannich bases of 4'-hydroxychalcones 2a-e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC-3 cell lines. Bioactivities of 2a-e, which are reported for the first time in this study, were compared against their precursor 4'-hydroxychalcones 1a-e. Compound 2b was found to be the most potent (IC(50 )= 3.7 microM) among the compounds synthesized. In addition, the compounds 1a-c and 2d showed moderate cytotoxicity. Incorporation of the 3'-piperidinomethyl group in 1b and 1d raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a-e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC-3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted.
Gul
Halise I
HI
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey. incigul@atauni.edu.tr
Yerdelen
Kadir O
KO
Gul
Mustafa
M
Das
Umashankar
U
Pandit
Bulbul
B
Li
Pui-Kai
PK
Secen
Hasan
H
Sahin
Fikrettin
F
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D007202:Indicators and Reagents; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D047188:Chalcones; D007202:Indicators and Reagents; D008352:Mannich Bases