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).
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Authors | Isabel Gomez-Monterrey, Giovanni Santelli, Pietro Campiglia, Daniela Califano, Fabiano Falasconi, Claudio Pisano, Loredana Vesci, Teresa Lama, Paolo Grieco, Ettore Novellino |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 48
Issue 4
Pg. 1152-7
(Feb 24 2005)
ISSN: 0022-2623 [Print] United States |
PMID | 15715481
(Publication Type: Journal Article)
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Chemical References |
- 3-(3-(N,N-dimethyl)aminopropyl)spiro((dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno(2,3-b)naphtho-4',9'-dione))
- Antineoplastic Agents
- Hydantoins
- Naphthoquinones
- Spiro Compounds
- Topoisomerase II Inhibitors
- Doxorubicin
- Cisplatin
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Topics |
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Cisplatin
(pharmacology)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
- Drug Screening Assays, Antitumor
- Humans
- Hydantoins
(chemical synthesis, chemistry, pharmacology)
- Molecular Conformation
- Naphthoquinones
(chemical synthesis, chemistry, pharmacology)
- Spiro Compounds
(chemical synthesis, chemistry, pharmacology)
- Stereoisomerism
- Structure-Activity Relationship
- Topoisomerase II Inhibitors
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