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).
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Line, Tumor
-
Cisplatin / pharmacology
-
Doxorubicin / pharmacology
-
Drug Resistance, Neoplasm
-
Drug Screening Assays, Antitumor
-
Humans
-
Hydantoins / chemical synthesis*
-
Hydantoins / chemistry
-
Hydantoins / pharmacology
-
Molecular Conformation
-
Naphthoquinones / chemical synthesis*
-
Naphthoquinones / chemistry
-
Naphthoquinones / pharmacology
-
Spiro Compounds / chemical synthesis*
-
Spiro Compounds / chemistry
-
Spiro Compounds / pharmacology
-
Stereoisomerism
-
Structure-Activity Relationship
-
Topoisomerase II Inhibitors
Substances
-
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