Galectin-inhibitory thiodigalactoside ester derivatives have antimigratory effects in cultured lung and prostate cancer cells.
Aromatic 3,3'-diesters of thiodigalactoside were synthesized in a rapid three-step sequence from commercially available thiodigalactoside and evaluated as inhibitors of cancer- and immunity-related galectins. For each of galectins-1, -3, -7, and -9N-terminal domain, aromatic 3,3'-diesters of thiodigalactoside were found to have affinities in the low micromolar range, which represents a 7-70 fold enhancement over thiodigalactoside itself. No significant improvement was found for galectin-8 N-terminal domain. Two of the compounds were selected for testing in cell culture and were shown to have potent antimigratory effects on human PC-3 prostate and human A549 nonsmall-cell lung cancer cells.
Delaine
Tamara
T
Organic Chemistry, Lund University, POB 124, SE-221 00 Lund, Sweden.
Cumpstey
Ian
I
Ingrassia
Laurent
L
Le Mercier
Marie
M
Okechukwu
Paul
P
Leffler
Hakon
H
Kiss
Robert
R
Nilsson
Ulf J
UJ
D045744:Cell Line, Tumor; D002465:Cell Movement; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D037161:Galectins / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008956:Models, Chemical; D011471:Prostatic Neoplasms / Q000628:therapy*; D017434:Protein Structure, Tertiary; D013862:Thiogalactosides / Q000737:chemistry / Q000378:metabolism*
D004952:Esters; D037161:Galectins; D013862:Thiogalactosides; C031803:thiodigalactoside