Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system.
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).
Gomez-Monterrey
Isabel
I
Dipartimento di Chimica Farmaceutica e Tossicologica, University of Naples Federico II, Napoli, Italy.
Santelli
Giovanni
G
Campiglia
Pietro
P
Califano
Daniela
D
Falasconi
Fabiano
F
Pisano
Claudio
C
Vesci
Loredana
L
Lama
Teresa
T
Grieco
Paolo
P
Novellino
Ettore
E
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
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