title: Cinnamoyl nitrogen mustard derivatives of pyrazole analogues of tallimustine modified at the amidino moiety: design, synthesis, molecular modeling and antitumor activity studies.
abstract: The design, synthesis and in vitro activities of a series of cinnamoyl nitrogen mustard pyrazole analogues of tallimustine 8-13, in which the amidino moiety has been replaced by moieties of different physico-chemical features are described, and the structure-activity relationships are discussed. In spite of the relevance of these modifications on the amidino moiety, these derivatives showed significant growth inhibitory activity against mouse leukemia L1210 cells. A selected series of compounds have been evaluated for their sequence selective alkylating properties and cytotoxicity against human K562 leukemia cells. Therefore, the presence of the amidino moiety, and in general of a basic moiety, is not an absolute requirement for biological activity. Our preliminary results indicated that the compounds of this series have a pattern of alkylation similar to that of tallimustine, but they seem to be less reactive overall in alkylating naked DNA.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. brlpgv@unife.it
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Italo
authors.initials: I
authors.lastname: Beria
authors.forename: Paolo
authors.initials: P
authors.lastname: Cozzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Geroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
authors.forename: John P
authors.initials: JP
authors.lastname: Bingham
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004214:Distamycins / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004214:Distamycins; D009588:Nitrogen Mustard Compounds; D011720:Pyrazoles; C066900:tallimustine; D004247:DNA