title: Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and adozelesin.
abstract: Two pyrazole analogs structurally related to the antitumor agents adozelesin and U-71,184 respectively were synthesized. By using a polymerase chain reaction approach, both compounds show selective binding to A + T rich sequences exactly as reference compound U-71,184. In in vitro assays, against L1210 cell lines, both derivatives showed cytotoxicity in the pM range, values comparable with the natural target compound (+)-CC-1065. The most active compound showed very high antitumor activity in mice implanted with L1210 cells (ILS% 363).
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Italy. pgb@dns.unife.it
authors.forename: P G
authors.initials: PG
authors.lastname: Baraldi
authors.forename: B
authors.initials: B
authors.lastname: Cacciari
authors.forename: R
authors.initials: R
authors.lastname: Romagnoli
authors.forename: G
authors.initials: G
authors.lastname: Spalluto
authors.forename: R
authors.initials: R
authors.lastname: Gambari
authors.forename: N
authors.initials: N
authors.lastname: Bianchi
authors.forename: M
authors.initials: M
authors.lastname: Passadore
authors.forename: P
authors.initials: P
authors.lastname: Ambrosino
authors.forename: N
authors.initials: N
authors.lastname: Mongelli
authors.forename: P
authors.initials: P
authors.lastname: Cozzi
authors.forename: C
authors.initials: C
authors.lastname: Geroni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D001572:Benzofurans; D001665:Binding Sites; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D053138:Cyclohexenes; D000080890:Duocarmycins; D007211:Indoles / Q000737:chemistry*; D007939:Leukemia L1210 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013055:Spectrophotometry, Infrared
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D003509:Cyclohexanecarboxylic Acids; D053138:Cyclohexenes; D000080890:Duocarmycins; D007211:Indoles; D011720:Pyrazoles; C054483:U 71184; C060090:adozelesin