Synthesis of a novel C2/C2′-exo unsaturated pyrrolobenzodiazepine cross-linking agent with remarkable DNA binding affinity and cytotoxicity

被引：39

作者：

Gregson, SJ

Howard, PW

Jenkins, TC

Kelland, LR

Thurston, DE

机构：

[1] Univ Portsmouth, CRC Gene Targeted Drug Design Res Grp, Sch Pharm & Biomed Sci, Portsmouth PO1 2DT, Hants, England

[2] Univ Greenwich, Sch Chem & Life Sci, London SE18 6PF, England

[3] CRC Ctr Canc Therapeut, Canc Res Inst, Sutton SM2 5PX, Surrey, England

来源：

CHEMICAL COMMUNICATIONS | 1999年 / 09期

关键词：

D O I：

10.1039/a809791g

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A C2/C2'-exo unsaturated pyrrolobenzodiazepine dimer 1 has been synthesised which is cytotoxic at the picomolar level and has remarkable covalent DNA binding affinity, raising the melting temperature of duplex-form calf thymus DNA by 34 degrees C after 18 h incubation.

引用

页码：797 / 798

页数：2

共 17 条

[1] RATIONAL DESIGN OF A HIGHLY EFFICIENT IRREVERSIBLE DNA INTERSTRAND CROSS-LINKING AGENT BASED ON THE PYRROLOBENZODIAZEPINE RING-SYSTEM [J].

BOSE, DS ;

THOMPSON, AS ;

CHING, JS ;

HARTLEY, JA ;

BERARDINI, MD ;

JENKINS, TC ;

NEIDLE, S ;

HURLEY, LH ;

THURSTON, DE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (12) :4939-4941

[2] SELECTIVE CLEAVAGE OF THE ALLYL AND ALLYLOXCARBONYL GROUPS THROUGH PALLADIUM-CATALYZED HYDROSTANNOLYSIS WITH TRIBUTYLTIN HYDRIDE - APPLICATION TO THE SELECTIVE PROTECTION-DEPROTECTION OF AMINO-ACID DERIVATIVES AND IN PEPTIDE-SYNTHESIS [J].

DANGLES, O ;

GUIBE, F ;

BALAVOINE, G ;

LAVIELLE, S ;

MARQUET, A .

JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (22) :4984-4993

[3] MILD PALLADIUM (0)-CATALYZED DEPROTECTION OF ALLYL ESTERS - A USEFUL APPLICATION IN THE SYNTHESIS OF CARBAPENEMS AND OTHER BETA-LACTAM DERIVATIVES [J].

DEZIEL, R .

TETRAHEDRON LETTERS, 1987, 28 (38) :4371-4372

[4] TOTAL SYNTHESIS OF (+)-POROTHRAMYCIN-B [J].

FUKUYAMA, T ;

LIU, G ;

LINTON, SD ;

LIN, SC ;

NISHINO, H .

TETRAHEDRON LETTERS, 1993, 34 (16) :2577-2580

[5] STRUCTURE OF A COVALENT DNA MINOR-GROOVE ADDUCT WITH A PYRROLOBENZODIAZEPINE DIMER - EVIDENCE FOR SEQUENCE-SPECIFIC INTERSTRAND CROSS-LINKING [J].

JENKINS, TC ;

HURLEY, LH ;

NEIDLE, S ;

THURSTON, DE .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (26) :4529-4537

[6]

JONES GB, 1990, ANTI-CANCER DRUG DES, V5, P249

[7] A VERSATILE AND EFFICIENT SYNTHESIS OF CARBINOLAMINE-CONTAINING PYRROLO[1,4]BENZODIAZEPINES VIA THE CYCLIZATION OF N-(2-AMINOBENZOYL)PYRROLIDINE-2-CARBOXALDEHYDE DIETHYL THIOACETALS - TOTAL SYNTHESIS OF PROTHRACARCIN [J].

LANGLEY, DR ;

THURSTON, DE .

JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (01) :91-97

[8] TOTAL SYNTHESES OF (+/-)-CRININE AND (+/-)-BUPHANISINE [J].

MARTIN, SF ;

CAMPBELL, CL .

JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (14) :3184-3190

[9]

MURATA M, 1989, Patent No. 891028599

[10] THE RELEVANCE OF DRUG-DNA SEQUENCE SPECIFICITY TO ANTITUMOR-ACTIVITY [J].

NEIDLE, S ;

PUVVADA, MS ;

THURSTON, DE .

EUROPEAN JOURNAL OF CANCER, 1994, 30A (04) :567-568

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