Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters

被引：34

作者：

Koutsourea, Anna I. ^{[1
]}

Fousteris, Manolis A. ^{[1
]}

Arsenou, Evagelia S. ^{[1
]}

Papageorgiou, Athanasios ^{[2
]}

Pairas, George N. ^{[1
]}

Nikolaropoulos, Sotiris S. ^{[1
]}

机构：

[1] Univ Patras, Dept Pharm, Sch Hlth Sci, Med Chem Lab, Patras 26500, Greece

[2] Theagenion Anticanc Hosp, Lab Expt Chemotherapy, Thessaloniki, Greece

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 09期

关键词：

steroids; nitrogen mustards; antileukemic activity; SAR;

D O I：

10.1016/j.bmc.2008.03.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The synthesis and the in vivo evaluation against leukemias P388 and L1210 of six new alkylating steroidal esters are described. The esteric derivatives incorporating the 17 beta-acetamido-B-lactamic steroidal skeleton exhibited increased antileukemic activity and lower toxicity, compared to the 17 beta-acetamido-7-keto analogs. Among the 17 beta-acetamido-B-lactamic steroidal esters, the most potent compound afforded four out of six cures in leukemia P388 and was measured to be almost non-toxic, producing significant low levels of toxicity. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5207 / 5215

页数：9

共 48 条

[31] Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand [J].

Marquis, JC ;

Hillier, SM ;

Dinaut, AN ;

Rodrigues, D ;

Mitra, K ;

Essigmann, JM ;

Croy, RG .

CHEMISTRY & BIOLOGY, 2005, 12 (07) :779-787

[32] PHARMACOKINETICS AND METABOLISM OF CHLORAMBUCIL IN PATIENTS WITH MALIGNANT DISEASE [J].

MCLEAN, A ;

WOODS, RL ;

CATOVSKY, D ;

FARMER, P .

CANCER TREATMENT REVIEWS, 1979, 6 :33-&

[33] Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway [J].

Middleton, MR ;

Margison, GP .

LANCET ONCOLOGY, 2003, 4 (01) :37-44

[34] POTENTIAL ANTICANCER AGENTS .4. NITROGEN MUSTARDS OF METHYLBENZOIC ACIDS [J].

NICULESCUDUVAZ, I ;

IONESCU, M ;

CAMBANIS, A ;

VITAN, M ;

FEYNS, V .

JOURNAL OF MEDICINAL CHEMISTRY, 1968, 11 (03) :500-+

[35]

Nikolaropoulos S, 2000, ANTICANCER RES, V20, P2745

[36]

Nikolaropoulos SS, 1997, ANTICANCER RES, V17, P4525

[37] Structure-anti-leukemic activity relationship study of B- and D-ring modified and non-modified steroidal esters of chlorambucil's active metabolite [J].

Papageorgiou, A ;

Koutsourea, AI ;

Arsenou, ES ;

Fousteris, MA ;

Mourelatos, D ;

Nikolaropoulos, SS .

ANTI-CANCER DRUGS, 2005, 16 (10) :1075-1082

[38]

PARSONS PG, 1981, CANCER RES, V41, P1525

[39] Reactions of 4-bis(2-chloroethyl)aminophenylacetic acid (phenylacetic acid mustard) in physiological solutions [J].

Pettersson-Fernholm, T ;

Vilpo, J ;

Kosonen, M ;

Hakala, K ;

Hovinen, J .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1999, (10) :2183-2187

[40] DNA cross-linking agents as antitumor drugs [J].

Rajski, SR ;

Williams, RM .

CHEMICAL REVIEWS, 1998, 98 (08) :2723-2795

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