Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates

被引：120

作者：

Bhattacharjee, AK ^{[1
]}

Hartell, MG ^{[1
]}

Nichols, DA ^{[1
]}

Hicks, RP ^{[1
]}

Stanton, B ^{[1
]}

van Hamont, JE ^{[1
]}

Milhous, WK ^{[1
]}

机构：

[1] Walter Reed Army Inst Res, Div Expt Therapeut, Dept Med Chem, Silver Spring, MD 20910 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 39卷 / 01期

关键词：

QSAR; pharmacophore; malaria;

D O I：

10.1016/j.ejmech.2003.10.004

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A widely applicable three-dimensional QSAR pharmacophore model for antimalarial activity was developed from a set of 17 substituted antimalarial indolo[2,1-b]quinazoline-6,12-diones (tryptanthrins) that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plasmodium falciparum malaria. The pharmacophore, which contains two hydrogen bond acceptors (lipid) and two hydrophobic (aromatic) features, was found to map well onto many well-known antimalarial drug classes including quinolines, chalcones, rhodamine dyes, Pfmrk cyclin dependent kinase inhibitors, malarial FabH inhibitors, and plasmepsin inhibitors. The phamacophore allowed searches for new antimalarial candidates from multiconformer 3D databases and enabled custom designed synthesis of new potent analogues. (C) 2003 Elsevier SAS. All rights reserved.

引用

页码：59 / 67

页数：9

共 29 条

[1]

*ACC INC, 2000, CATALYST VERS 4 5 SO

[2]

[Anonymous], CHEM INF SYST

[3]

Baker W.R., 1995, Patent, Patent No. [5441955, US5441955A]

[4] Molecular electronic properties of a series of 4-quinolinecarbinolamines define antimalarial activity profile [J].

Bhattacharjee, AK ;

Karle, JM .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (23) :4622-4629

[5] Analysis of stereoelectronic properties, mechanism of action and pharmacophore of synthetic indolo[2,1-b]quinazoline-6,12-dione derivatives in relation to antileishmanial activity using quantum chemical, cyclic voltammetry and 3-D-QSAR CATALYST procedures [J].

Bhattacharjee, AK ;

Skanchy, DJ ;

Jennings, B ;

Hudson, TH ;

Brendle, JJ ;

Werbovetz, KA .

BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (06) :1979-1989

[6] A 3D QSAR pharmacophore model and quantum chemical structure-activity analysis of chloroquine(CQ)-resistance reversal [J].

Bhattacharjee, AK ;

Kyle, DE ;

Vennerstrom, JL ;

Milhous, WK .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2002, 42 (05) :1212-1220

[7] Stereoelectronic properties of antimalarial artemisinin analogues in relation to neurotoxicity [J].

Bhattacharjee, AK ;

Karle, JM .

CHEMICAL RESEARCH IN TOXICOLOGY, 1999, 12 (05) :422-428

[8] PLASMODIUM-FALCIPARUM - ASSESSMENT OF INVITRO GROWTH BY [H-3]-LABELED HYPOXANTHINE INCORPORATION [J].

CHULAY, JD ;

HAYNES, JD ;

DIGGS, CL .

EXPERIMENTAL PARASITOLOGY, 1983, 55 (01) :138-146

[9] First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling [J].

Daines, RA ;

Pendrak, I ;

Sham, K ;

Van Aller, GS ;

Konstantinidis, AK ;

Lonsdale, JT ;

Janson, CA ;

Qiu, XY ;

Brandt, M ;

Khandekar, SS ;

Silverman, C ;

Head, MS .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (01) :5-8

[10] QUANTITATIVE ASSESSMENT OF ANTI-MALARIAL ACTIVITY INVITRO BY A SEMIAUTOMATED MICRODILUTION TECHNIQUE [J].

DESJARDINS, RE ;

CANFIELD, CJ ;

HAYNES, JD ;

CHULAY, JD .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1979, 16 (06) :710-718

← 1 2 3 →