Novel benzoyl nitrogen mustard derivatives of pyrazole analogues of distamycin A: synthesis and antileukemic activity.
The design and synthesis of novel benzoic acid mustard (BAM) derivatives of distamycin A bearing one or more pyrazole rings replacing the pyrrole rings of the latter are described. In vitro and in vivo activities against L1210 leukemia are reported and discussed. Some of these compounds show an activity profile comparable to tallimustine 1. All the compounds bearing the pyrazole ring close to the BAM moiety show reduced cytotoxicity in comparison to derivatives characterized by the BAM linked to a pyrrole: the same effect has not been observed when occurring at the amidine terminus of the oligopeptidic frame.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@ifeuniv.unife.it
Cozzi
P
P
Geroni
C
C
Mongelli
N
N
Romagnoli
R
R
Spalluto
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D004214:Distamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D020128:Inhibitory Concentration 50; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008956:Models, Chemical; D009150:Mustard Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013534:Survival; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004214:Distamycins; D009150:Mustard Compounds; D009588:Nitrogen Mustard Compounds; D011720:Pyrazoles; C031280:pyrazole; C066900:tallimustine; C030000:stallimycin