Synthesis and antitumor activity of 7-ethyl-9-alkyl derivatives of camptothecin

被引：18

作者：

Gao, HY ^{[1
]}

Zhang, XW ^{[1
]}

Chen, Y ^{[1
]}

Shen, HW ^{[1
]}

Sun, J ^{[1
]}

Huang, M ^{[1
]}

Ding, J ^{[1
]}

Li, C ^{[1
]}

Lu, W ^{[1
]}

机构：

[1] Chinese Acad Sci, Grad Sch, Shanghai Inst Mat Med, SIBS, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 08期

关键词：

camptothecin; topoisomerase I; antitumor activity;

D O I：

10.1016/j.bmcl.2005.02.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A series of new camptothecin derivatives, as topoisomerase I inhibitor, were synthesized to identify potent antitumor agents. The synthesis method was based on the Claisen rearrangement of 10-allyloxy-7-ethylcamptothecin. All of the compounds were assayed for cytotoxicity against two human tumor cell lines, Bel7402, HCT116, and showed good potency in vitro. Compounds 2, 4, 9, were assessed for the stability of lactone in human plasma. And then compound 2 was tested for antitumor activity in vitro against mouse tumor sarcoma-180. The results suggested that the small alkyl groups in the both 7- and 9-positions of camptothecin could promote liposolubility, antitumor activity in vitro and vivo, though did not bring much increase of the stability of lactone. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2003 / 2006

页数：4

共 15 条

[1]

The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity [J].

Bom, D ;

Curran, DP ;

Kruszewski, S ;

Zimmer, SG ;

Strode, JT ;

Kohlhagen, G ;

Du, W ;

Chavan, AJ ;

Fraley, KA ;

Bingcang, AL ;

Latus, LJ ;

Pommier, Y ;

Burke, TG .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (21) :3970-3980

[2]

A STEREOSELECTIVE TOTAL SYNTHESIS OF (+/-)-MUZIGADIAL [J].

BOSCH, MP ;

CAMPS, F ;

COLL, J ;

GUERRERO, A ;

TATSUOKA, T ;

MEINWALD, J .

JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (06) :773-784

[3]

CAI JC, 1981, ACTA CHIM SINICA, V39, P171

[4]

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity [J].

Dallavalle, S ;

Ferrari, A ;

Biasotti, B ;

Merlini, L ;

Penco, S ;

Gallo, G ;

Marzi, M ;

Tinti, MO ;

Martinelli, R ;

Pisano, C ;

Carminati, P ;

Carenini, N ;

Beretta, G ;

Perego, P ;

De Cesare, M ;

Pratesi, G ;

Zunino, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (20) :3264-3274

[5]

CONVERSION OF CHIRAL AMINO-ACIDS TO ENANTIOMERICALLY PURE ALPHA-METHYLAMINES [J].

DONNER, BG .

TETRAHEDRON LETTERS, 1995, 36 (08) :1223-1226

[6]

Giles FJ, 2002, CLIN CANCER RES, V8, P2134

[7]

HSIANG YH, 1985, J BIOL CHEM, V260, P4873

[8]

Homocamptothecins:: Synthesis and antitumor activity of novel E-ring-modified camptothecin analogues [J].

Lavergne, O ;

Lesueur-Ginot, L ;

Rodas, FP ;

Kasprzyk, PG ;

Pommier, J ;

Demarquay, D ;

Prévost, G ;

Ulibarri, G ;

Rolland, A ;

Schiano-Liberatore, AM ;

Harnett, J ;

Pons, D ;

Camara, J ;

Bigg, DCH .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (27) :5410-5419

[9]

Lee JH, 2000, ANN NY ACAD SCI, V922, P324

[10]

LU W, 2003, Patent No. 2004000490

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