Cheng, Hao published the artcileSynthesis and Enzyme-Specific Activation of Carbohydrate-Geldanamycin Conjugates with Potent Anticancer Activity, Product Details of C13H19NO3, the main research area is glycosylation enzyme prodrug therapy galactosidase synthesis geldanamycin antitumor monosaccharide; human geldanamycin synthesis anticancer antibiotic Hsp90 glucosidase inhibitor hydroxymethydihydroxypyrrolidine.
Geldanamycin (GA) is a potent anticancer antibiotic that inhibits Hsp90. Its potential clin. utility is hampered by its severe toxicity. To alleviate this problem, we synthesized a series of carbohydrate-geldanamycin conjugates for enzyme-specific activation to increase tumor selectivity. The conjugation was carried out at the C-17-position of GA. Their anticancer activity was tested in a number of cancer cell lines. The enzyme-specific activation of these conjugates was evaluated with β-galactosidase and β-glucosidase. Evidently, glycosylation of C-17-position converted GA to an inactive prodrug before enzyme cleavage. Glucose-GA, as pos. control, showed anticancer activity with IC50 of 70.2-380.9 nM in various cancer cells by β-glucosidase activation inside of the tumor cells, which was confirmed by 3-fold inhibition using β-glucosidase specific inhibitor [2,5-dihydroxymethy-3,4-dihydroxypyrrolidine (DMDP)]. Compared to glucose-GA, galactose- and lactose-GA conjugates exhibited much less activity with IC50 greater than 8000-25 000 nM. However, when galactose- and lactose-GA were incubated with β-galactosidase in the cells, their anticancer activity was enhanced by 3- to 40-fold. The results suggest that GA can be inactivated by glycosylation of C-17-position and reactivated for anticancer activity by β-galactosidase. Therefore, galactose-GA can be exploited in antibody-directed enzyme prodrug therapy (ADEPT) with β-galactosidase for enzyme-specific activation in tumors to increase tumor selectivity.
Journal of Medicinal Chemistry published new progress about Antibiotics. 87905-98-4 belongs to class alcohols-buliding-blocks, name is Benzyl (5-hydroxypentyl)carbamate, and the molecular formula is C13H19NO3, Product Details of C13H19NO3.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts