title: Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system.
abstract: The synthesis and cytotoxic evaluation of 3-(alkyl)(alkyl-substituted)spiro[(dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)]derivatives are described. Evaluation of these analogues against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines uncovered for most of the compounds a cytotoxic potency comparable to or greater than that of doxorubicin. Compound 15 exhibited remarkable cytotoxic activity against several other human solid tumor cell lines. Interestingly, only a partial cross-resistance to compound 15 in selected tumor cell sublines known to be resistant to doxorubicin (MCF-7/Dx and A2780/Dx) was observed, whereas a total absence of cross-resistance in a tumor cell subline selected for resistance to cisplatin was found (A2780/DDP).
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, University of Naples Federico II, Napoli, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Giovanni
authors.initials: G
authors.lastname: Santelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Daniela
authors.initials: D
authors.lastname: Califano
authors.forename: Fabiano
authors.initials: F
authors.lastname: Falasconi
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.forename: Loredana
authors.initials: L
authors.lastname: Vesci
authors.forename: Teresa
authors.initials: T
authors.lastname: Lama
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: C498568:3-(3-(N,N-dimethyl)aminopropyl)spiro((dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno(2,3-b)naphtho-4',9'-dione)); D000970:Antineoplastic Agents; D006827:Hydantoins; D009285:Naphthoquinones; D013141:Spiro Compounds; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin; D002945:Cisplatin