Camptothecin-7-yl-methanthiole: Semisynthesis and Biological Evaluation

被引：19

作者：

Christodoulou, Michael S. ^{[1
]}

Zunino, Franco ^{[2
]}

Zuco, Valentina ^{[2
]}

Borrelli, Stella ^{[1
]}

Comi, Daniela ^{[1
]}

Fontana, Gabriele ^{[3
]}

Martinelli, Marisa ^{[4
]}

Lorens, James B. ^{[5
]}

Evensen, Lasse ^{[5
]}

Sironi, Maurizio ^{[1
]}

Pieraccini, Stefano ^{[1
]}

Dalla Via, Lisa ^{[6
]}

Gia, Ornella Maria ^{[6
]}

Passarella, Daniele ^{[1
]}

机构：

[1] Univ Milan, Dipartimento Chim, I-20133 Milan, Italy

[2] Fdn IRCCS Ist Nazl Studio & Cura Tumori, I-20133 Milan, Italy

[3] Indena SPA, I-20141 Milan, Italy

[4] NiKem Res Srl, Dept Med Chem, I-20021 Baranzate Di Bollate, Italy

[5] Univ Bergen, Dept Biomed, N-5020 Bergen, Norway

[6] Univ Padua, Dipartimento Sci Farmaco, I-35131 Padua, Italy

来源：

CHEMMEDCHEM | 2012年 / 7卷 / 12期

关键词：

angiogenesis; anticancer agents; camptothecin; inhibitors; topoisomerases; PROTEIN-KINASE-C; MULTISUBSTRATE ANALOG INHIBITORS; MICROWAVE-ASSISTED SYNTHESIS; SOLID-PHASE SYNTHESIS; DRUG TARGETS; BISUBSTRATE INHIBITORS; CYCLOADDITION REACTION; CATALYTIC MECHANISM; CRYSTAL-STRUCTURE; TERMINAL ALKYNES;

D O I：

10.1002/cmdc.201200322

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.

引用

页码：2134 / 2143

页数：10

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