DNA sequence-recognizing properties of minor groove alkylating agents. Effects of the replacement of N-methylpyrrole by an N-methylimidazole on tallimustine and its own homologue.
The linkage of an heterocycle, like N-methylimidazole, to minor DNA groove binders containing two or three pyrroles lead to a new class of oligopeptides with reduced antitumor activity both in vitro and in vivo if compared to tallimustine (CAS 115308-98-0) and its tetrapyrrole homologue 9. In the present paper is reported the correlation between the cytoxicity of tallimustine and its derivatives 9-11 with their ability to inhibit polymerase chain reaction (PCR) amplification of oestrogen receptor and Ha-ras gene sequences, containing A + T rich and G + C rich regions, respectively. Tallimustine and its tetrapyrrole homologue 9 were found to have higher sequence selectivity for the human oestrogen receptor (ER) gene with respect to the relative imidazole-containing analogues.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@dns.unife.it
Romagnoli
R
R
Spalluto
G
G
Cozzi
P
P
Mongelli
N
N
Bianchi
N
N
Gambari
R
R
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004214:Distamycins / Q000494:pharmacology*; D005260:Female; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D017931:DNA Primers; D004214:Distamycins; D007093:Imidazoles; D009588:Nitrogen Mustard Compounds; D011758:Pyrroles; D011960:Receptors, Estrogen; C066900:tallimustine; D004247:DNA; C096654:N-methylpyrrole; C018100:1-methylimidazole