• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.169-173
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• 2003

Alkylthioureido-1,3-propandiols (KY353X series) were synthesized and evaluated as inhibitors for neutral sphingomyelinase (N-SMase). To examine whether KY353X series inhibit N-SMase, we purified the N-SMase from bovine brain. The N-SMase was partially purified by sequential chromatographies of DEAE-Cellulose anionic exchange and phenyl-5PW hydrophobic HPLC. These seqeuntial procedures for N-SMase resulted in a 67-fold purification and excluded other isoforms of SMase. Based on in vitro assay, KY353X series inhibited N-SMase activity in time, concentration-dependent manners and completely inactivated N-SMase at 50 $\mu$M. In particular, KY3535 and KY3536 inhibited more effectively than the others. To further determine the .inhibitory pattern, a Dixon plot was constructed, to showing that the inhibition by KY3535 and KY3536 were competitive. The inhibition constant (Ki) of KY3535 and KY3536 was 1.7 $\mu$M and 2.5$\mu$M in 100 mM Tris-HCl buffer, pH 7.0, respectively.

• YAKHAK HOEJI
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• v.48 no.5
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• pp.272-277
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• 2004

The 2-amino-l-phenylpropanols 4∼7 were reacted with isothiocyanates to afford the 20 thioureido MAPP derivatives 8a∼11e, which were tested their cytotoxic activity by MTT assay. The cytotoxicity of alkylthioureido compounds were increased and decreased by alkyl chain length from $C_{8}$ to $C_{14}$ and of phenylthioureido compounds showed poor activity. The compounds (8b, 8c, 9b, 9c, l0b, 10c, 11b, 11c) with $C_{10}$ and $C_{12}$ alkyl chains gave stronger activity than reference compound B13. The $IC_{50}$/ of compound 8c was 1.05$\mu$M and 3 times stronger activity than B13. The stereochemistry of synthesized compounds affected very little to cytotoxic activity.