Thio-sugars VII. Effect of 3-deoxy-4-S-(beta-D-gluco- and beta-D-galactopyranosyl)-4-thiodisaccharides and their sulfoxides and sulfones on the viability and growth of selected murine and human tumor cell lines.
The first conversion of (1-->4)-thiodisaccharides into corresponding sulfoxides and sulfones by conventional oxidation with m-chloroperoxybenzoic acid (MCPBA) is reported. The effects of alpha-(1-->4)-3'-deoxythiodisaccharides (8-9) and their sulfoxide (14-15) and sulfone (16-17) derivatives on murine leukemia and human colon and pancreatic carcinoma cell viability were studied. Concentrations of thio-sugars that decreased tumor cell line viability by 50% (IC(50)), measured via the MTT assay, ranged from 6.4 to 38.3 microg/mL. The effect of alpha-(1-->4)-3'-deoxythiodisaccharide derivatives were most profound on human pancreatic epithelial carcinoma (PANC-1) cells with compounds 8 and 9 having IC(50) values of 6.4 microg/mL and 8.2 microg/mL, respectively. Sulfone derivatives 16 and 17 also had pronounced effects on PANC-1 cell viability (IC(50)=10.2 microg/mL and 9.6 microg/mL, respectively). These results indicate that deoxythio-disaccharide analogs generated by functionalization of the universal chiral precursor levoglucosenone may have cytotoxic properties and therapeutic potential as anticancer agents.
Witczak
Zbigniew J
ZJ
Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA 18766, USA. witczak@wilkes.edu
Kaplon
Peter
P
Dey
P Markus
PM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology; D013454:Sulfoxides / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002241:Carbohydrates; D013438:Sulfhydryl Compounds; D013450:Sulfones; D013454:Sulfoxides