Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system

被引：50

作者：

Gomez-Monterrey, I

Santelli, G

Campiglia, P

Califano, D

Falasconi, F

Pisano, C

Vesci, L

Lama, T

Grieco, P

Novellino, E

机构：

[1] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[2] Ist Tumori Fondaz G Pascale, Naples, Italy

[3] R&S Sigma Tau SpA, Area Ric Oncol, Rome, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 04期

关键词：

D O I：

10.1021/jm0408565

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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).

引用

收藏

页码：1152 / 1157

页数：6

相关论文

共 18 条

[1] THE DESIGN, SYNTHESIS AND DEVELOPMENT OF A NEW CLASS OF POTENT ANTINEOPLASTIC ANTHRAQUINONES [J].

CHENG, CC ;

ZEECHENG, RKY .

PROGRESS IN MEDICINAL CHEMISTRY, 1983, 20 :83-118

[2] SYNTHESIS, MOLECULAR MODELING, DNA-BINDING, AND ANTITUMOR PROPERTIES OF SOME SUBSTITUTED AMIDOANTHRAQUINONES [J].

COLLIER, DA ;

NEIDLE, S .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (04) :847-857

[3]

DENY WA, 1989, ANTI-CANCER DRUG DES, V4, P241

[4] CHROMOPHORE-MODIFIED ANTITUMOR ANTHRACENEDIONES - SYNTHESIS, DNA-BINDING, AND CYTOTOXIC ACTIVITY OF 1,4-BIS[(AMINOALKYL)AMINO]BENZO[G]-PHTHALAZINE-5,10-DIONES [J].

GANDOLFI, CA ;

BEGGIOLIN, G ;

MENTA, E ;

PALUMBO, M ;

SISSI, C ;

SPINELLI, S ;

JOHNSON, F .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (03) :526-536

[5] Peptidyl anthraquinones as potential antineoplastic drugs: Synthesis, DNA binding, redox cycling, and biological activity [J].

Gatto, B ;

Zagotto, G ;

Sissi, C ;

Cera, C ;

Uriarte, E ;

Palu, G ;

Capranico, G ;

Palumbo, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (16) :3114-3122

[6] New benzo[g]isoquinoline-5,10-diones and dihydrothieno [2,3-b]naphtho-4,9-dione derivatives:: Synthesis and biological evaluation as potential antitumoral agents [J].

Gomez-Monterrey, I ;

Campiglia, P ;

Grieco, P ;

Diurno, MV ;

Bolognese, A ;

La Colla, P ;

Novellino, E .

BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (17) :3769-3775

[7] Cycloaddition reactions of thiazolidine derivatives. An approach to the synthesis of new functionalized heterocyclic systems [J].

Gomez-Monterrey, IM ;

Campiglia, P ;

Mazzoni, O ;

Novellino, E ;

Diurno, MV .

TETRAHEDRON LETTERS, 2001, 42 (33) :5755-5757

[8]

Kohn KW, 1996, CANCER RES, V56, P5533

[9] HETEROSUBSTITUTED ANTHRACENE-9,10-DIONE ANALOGS - THE SYNTHESIS AND ANTITUMOR EVALUATION OF 5,8-BIS[(AMINOALKYL)AMINO]NAPHTHO[2,3-B]THIOPHENE-4,9-DIONES [J].

KRAPCHO, AP ;

PETRY, ME ;

HACKER, MP .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2651-2655

[10] Synthesis and antitumor evaluation of 2,5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-anthrapyrazoles) [J].

Krapcho, AP ;

Menta, E ;

Oliva, A ;

Di Domenico, R ;

Fiocchi, L ;

Maresch, ME ;

Gallagher, CE ;

Hacker, MP ;

Beggiolin, G ;

Giuliani, FC ;

Pezzoni, G ;

Spinelli, S .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (27) :5429-5444