Hybrid molecules between distamycin A and active moieties of antitumor agents.
The DNA minor groove is an attractive target for the design and development of molecules able to specifically recognize predetermined DNA sequences. The pyrrole-amide skeleton of distamycin A has been also used as DNA sequence selective vehicle for the delivery of alkylating functions to DNA targets. Selectivity for specific sequences may be of particular importance in affecting the activity of regulatory genes (oncogenes and tumor suppressor genes). Recent work on a number of hybrid compounds, in which known antitumor compounds or simple active moieties of known antitumor agents have been tethered to distamycin frame or hairpin polyamides derived from distamycin, is reviewed. The DNA alkylating and growth inhibition activities against several tumor cell lines are reported and discussed in terms of their structural differences in relation to both the number of N-methyl pyrrolic rings and the type of the alkylating unit tethered to the oligopyrrolic frame.
Baraldi
Pier Giovanni
PG
University of Ferrara, Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy. baraldi@unife.it
Preti
Delia
D
Fruttarolo
Francesca
F
Tabrizi
Mojgan Aghazadeh
MA
Romagnoli
Romeo
R
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004214:Distamycins / Q000737:chemistry*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004214:Distamycins; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; C029899:imidazole; C030000:stallimycin; D004247:DNA