title: Synthesis and in-vitro cytotoxicity evaluation of novel naphtindolizinedione derivatives, part II: improved activity for aza-analogues.
abstract: Our previous investigation on potential antitumor agents now got enriched by the evaluation of in-vitro activity against a full panel of NCI cancer cell lines for five new compounds. The concurrent presence in the molecular structure of a nitrogen atom in the aromatic system and a N,N-dimethylaminoethyl amide chain play a decisive role to enhance cytotoxicity. The N,N-anti compound 14 shows a higher activity than its N,N-syn isomer, exhibiting the best selective inhibition against the melanoma MALME-3M cell line, with a GI(50)-value (= 30 nM) corresponding to a 330-fold increase in activity compared to the corresponding deaza-analogue. Compound 14 is efficiently synthesized by aminolysis of the ester obtained as a single regio-isomer by an one-pot three-component procedure involving metal-assisted cyclization under microwave irradiation conditions.
authors.affiliation: Laboratorio di Chimica Bioorganica, Dipartimento di Fisica, Università degli studi di Trento, Povo Trento, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Defant
authors.forename: Graziano
authors.initials: G
authors.lastname: Guella
authors.forename: Ines
authors.initials: I
authors.lastname: Mancini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D054836:Indolizidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; D054836:Indolizidines