Abstract:
:In earlier investigations we have described the synthesis and biological evaluation of a panel of novel glycosylated heteroaromatics (1-12). It was found that these compounds can bind to DNA in vitro and are cytotoxic against several cancer cell lines at low micromolar concentration. We report here structure-activity studies of these molecules with respect to DNA binding and cytotoxicity. In particular the structure of the linker moiety between the carbohydrate and the intercalator, the stereochemistry at the anomeric position, and the substituents and stereochemistry at C-4 in one of the carbohydrate residues (4-amino-2,3,4,6-tetradeoxy-α-L-threo-hexopyranose) are investigated. All these structural features were identified to have a clear influence on DNA binding; however, only the substituents at C-4 in the carbohydrate residue exhibited an obvious impact on cytotoxicity. It was found that the amino group at C-4 was favored over all other substituents with regard to both DNA binding and cytotoxicity. The information gathered from these structure-activity investigations suggested that future work on the preparation of additional analogues should focus on molecules containing an amino sugar moiety.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Shi W,Lowary TLdoi
10.1016/j.bmc.2011.01.014subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1779-89issue
5eissn
0968-0896issn
1464-3391pii
S0968-0896(11)00030-7journal_volume
19pub_type
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