A new spacer group derived from arylmalonaldehydes for glucuronylated prodrugs
A new glucuronylated prodrug of doxorubicin, potentially useful for ADEPT or PMT cancer chemotherapy, has been prepared from 4-methyl phenyl malonaldehyde. The enol ether spacer, linked via a carbamate to the 3′-amino group of doxorubicin is rapidly cleaved by β-glucuronidase (E coli) at pH 7.2 and 37°C.
References (16)
- et al.
Biochemical Pharmacology
(1996) - et al.
Bioorg. Med. Chem. Lett.
(1997) - et al.
Tetrahedron
(1989) - et al.
Tetrahedron Lett.
(1997) - et al.
Chem. Abstr.
(1994) Drug Dev. Res.
(1995)- et al.
Curr. Med. Chem.
(1995)
Cited by (16)
β-Glucuronidase-responsive prodrugs for selective cancer chemotherapy: An update
2014, European Journal of Medicinal ChemistryCitation Excerpt :Thus, β-glucuronidase-responsive prodrugs of anthracyclines have received considerable attention over the past three decades to decrease the toxicity of this class of anticancer drugs towards healthy tissues [13,14,90,102–116]. Among them, DNR-GA3 [104,105], DOX-GA3 [108] and HMR 1826 [13,14,114,117] have been intensively investigated for their therapeutic activity in the course of a PMT (Fig. 10). These glucuronide prodrugs showed superior antitumor efficacy associated with reduced toxicity compared to standard chemotherapy.
Duocarmycin-based prodrugs for cancer prodrug monotherapy
2008, Bioorganic and Medicinal ChemistryA methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy
2004, Biochemical PharmacologyCitation Excerpt :We hypothesized that a methyl ester of DOX-GA3, DOX-mGA3, would be more lipophilic than DOX-GA3 and of better use in enzyme prodrug therapy. The methyl ester of other methylated glucuronide prodrugs has been reported to be hydrolyzed by carboxylesterases [12,13]. When administered in vivo, the methyl group of DOX-mGA3 might be removed by carboxylesterase activity in plasma to yield the original DOX-GA3 prodrug, which could in turn be activated by human β-glucuronidase (Fig. 1).
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