Purin-6-yl 6-deoxy-1-thio-beta-D-glucopyranoside. Enzymology, chemistry, and cytotoxicity.
Purin-6-yl 6-deoxy-1-thio-beta-D-glucopyranoside (4) is a substrate for almond beta-glucosidase and a weak competitive inhibitor of bovine liver beta-D-glucuronidase (Ki approximately 20mM). Both 4 and purine-protonated 4 undergo hydrolysis catalyzed by dilute acid in the pH range 0.17-2.59. These results are compared with those previously obtained with ammonium (purin-6-yl 1-thio-beta-D-glucopyranosid)uronate, (purin-6-yl 1-thio-beta-D-glucopyranosid)uronamide, purin-6-yl 1-thio-beta-D-glucopyranoside, and purin-6-yl 2-deoxy-1-thio-beta-D-glucopyranoside, and it is concluded that the data support an involvement of substituents at C-5 in producing productive Michaelis-complex conformers. The 6-deoxyglucoside is more active than the D-glucosiduronic acid in an L1210 mouse screen.
Zercher
C K
CK
Department of Medicinal Chemistry, State University of New York, Buffalo 14260.
Fedor
L R
LR
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005966:Glucuronidase / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D010944:Plants / Q000201:enzymology; D011355:Prodrugs / Q000627:therapeutic use; D013863:Thioglucosides / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D013865:Thioglycosides / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D011355:Prodrugs; D013863:Thioglucosides; D013865:Thioglycosides; C054022:6-purinyl 6-deoxy-1-thioglucopyranoside; D005966:Glucuronidase