TY - JOUR
T1 - Synthesis and structure-activity studies of some antitumor congeners of L-canaline
AU - Na Phuket, Supinan R.
AU - Trifonov, Latchezar S.
AU - Yu, Chongxi
AU - Worthen, David R.
AU - Crooks, Peter A.
AU - Rosenthal, Gerald A.
AU - Freeman, James W.
PY - 1999
Y1 - 1999
N2 - A number of congeners of the antitumor compound L-canaline, [L-2-amino- 4-(aminooxy)butyric acid], a structural analog of L-ornithine, have been synthesized and their growth-inhibitory effects evaluated in cultured MIA- PaCa-2 cells, a human pancreatic adenosarcoma, by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicate that L- canaline congeners in which the carbon chain length has been increased by one methylene unit exhibit a significant loss in cytotoxicity relative to the parent compound. Congeners in which the carbon chain length is decreased by one methylene unit retain the cytotoxicity of the parent compound against cultured MIA-PaCa-2 cells. Loss of the aminooxy or α-amino group of L- canaline severely curtails cell growth-inhibitory activity. With the exception of the n-octyl ester, esterification of α-canaline with simple a cobols has little effect on overall growth-inhibiting activity. It is noteworthy that the unnatural D-enantiomer of canaline is as deleterious to MIA-PaCa-2 cell growth as the naturally occurring L-enantiomer.
AB - A number of congeners of the antitumor compound L-canaline, [L-2-amino- 4-(aminooxy)butyric acid], a structural analog of L-ornithine, have been synthesized and their growth-inhibitory effects evaluated in cultured MIA- PaCa-2 cells, a human pancreatic adenosarcoma, by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. The results indicate that L- canaline congeners in which the carbon chain length has been increased by one methylene unit exhibit a significant loss in cytotoxicity relative to the parent compound. Congeners in which the carbon chain length is decreased by one methylene unit retain the cytotoxicity of the parent compound against cultured MIA-PaCa-2 cells. Loss of the aminooxy or α-amino group of L- canaline severely curtails cell growth-inhibitory activity. With the exception of the n-octyl ester, esterification of α-canaline with simple a cobols has little effect on overall growth-inhibiting activity. It is noteworthy that the unnatural D-enantiomer of canaline is as deleterious to MIA-PaCa-2 cell growth as the naturally occurring L-enantiomer.
KW - Chemotherapeutic agents
KW - L-canaline
KW - Pancreatic carcinoma
KW - Pyridoxal phosphate inhibitors
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U2 - 10.1002/(SICI)1098-2299(199908)47:4<170::AID-DDR3>3.0.CO;2-B
DO - 10.1002/(SICI)1098-2299(199908)47:4<170::AID-DDR3>3.0.CO;2-B
M3 - Article
AN - SCOPUS:0141721178
VL - 47
SP - 170
EP - 177
JO - Drug Development Research
JF - Drug Development Research
SN - 0272-4391
IS - 4
ER -