title: Pyrimido[4,5,6-kl]acridines. Synthesis, in vitro cytotoxicity and structure-activity relationships.
abstract: In a previous report we described the synthesis and biological properties of a group of pyrimido[4,5,6-kl]acridines 2, related to the pyrazolo[4,5,6-kl]acridines 1, promising antitumor agents possessing a broad spectrum of activity. Since the substitution of the pyrazole ring of the pyrazoloacridine chromophore with a pyrimidinone leads to derivatives that retain in vitro cytotoxic activity, we decided to further investigate the pyrimido[4,5 6-kl]acridines. Modifications at the ring system level, leading to chromophores with different characteristics, changes of substituent groups in position 6, simultaneous alteration of the chromophore and the introduction of a second cationic side chain in position 1 afforded 29 new pyrimido[4,5,6-kl]acridines, which were tested in vitro against the human colon adenocarcinoma HT29 cell line. Interesting structure-activity relationships could be drawn. Some selected derivatives were screened for their cytotoxic activity on the National Cancer Institute cell panel (60 human tumor lines).
authors.affiliation: Department of Chemical Sciences, University of Camerino, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Antonini
authors.forename: P
authors.initials: P
authors.lastname: Polucci
authors.forename: S
authors.initials: S
authors.lastname: Martelli
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines