Orally active esters of dihydroartemisinin:: Synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in mice

被引：41

作者：

Singh, Chandan ^{[1
]}

Chaudhary, Sandeep ^{[1
]}

Puri, Sunil K. ^{[2
]}

机构：

[1] Cent Drug Res Inst, Div Med & Proc Chem, Lucknow 226001, Uttar Pradesh, India

[2] Cent Drug Res Inst, Div Parasitol, Lucknow 226001, Uttar Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 04期

关键词：

D O I：

10.1016/j.bmcl.2007.12.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of artemisinin derived esters 7a-j, incorporating pharmacologically privileged substructure, such as biphenyl, adamantane and fluorene, have been prepared and evaluated for antimalarial activity against multidrug-resistant ( MDR) Plasmodium yoelii nigeriensis by oral route. Several of these compounds were found to be more active than the antimalarial drugs beta-arteether 4 and artesunic acid 5. Ester 7i, the most active compound of the series, provided 100% and 80% protection to the infected mice at 24 mg/kg x 4 days and 12 mg/kg x 4 days, respectively. In this model beta-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1436 / 1441

页数：6

共 27 条

[1]

Asthana O. P., 1997, Journal of Parasitic Diseases, V21, P1

[2] Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct modification of (+)-artemisinin and in vivo antimalarial screening of new, potential preclinical antimalarial candidates [J].

Avery, MA ;

Alvim-Gaston, M ;

Vroman, JA ;

Wu, B ;

Ager, A ;

Peters, W ;

Robinson, BL ;

Charman, W .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (19) :4321-4335

[3]

Bhattacharya AK, 1999, HETEROCYCLES, V51, P1681

[4] Antimalarial chemotherapeutic peroxides: artemisinin, yingzhaosu A and related compounds [J].

Borstnik, K ;

Paik, IH ;

Shapiro, TA ;

Posner, GH .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2002, 32 (13) :1661-1667

[5] ARTEETHER, A NEW ANTIMALARIAL DRUG - SYNTHESIS AND ANTIMALARIAL PROPERTIES [J].

BROSSI, A ;

VENUGOPALAN, B ;

GERPE, LD ;

YEH, HJC ;

FLIPPENANDERSON, JL ;

BUCHS, P ;

LUO, XD ;

MILHOUS, W ;

PETERS, W .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (03) :645-650

[6]

Cumming J N, 1997, Adv Pharmacol, V37, P253

[7] Orally active antimalarials:: Hydrolytically stable derivatives of 10-trifluoromethyl anhydrodihydroartemisinin [J].

Grellepois, F ;

Chorki, F ;

Ourévitch, M ;

Charneau, S ;

Grellier, P ;

McIntosh, KA ;

Charman, WN ;

Pradines, B ;

Crousse, B ;

Bonnet-Delpon, D ;

Bégué, JP .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (06) :1423-1433

[8]

Haynes RK, 2002, EUR J ORG CHEM, V2002, P113

[9] Mechanism-based design of parasite-targeted artemisinin derivatives: Synthesis and antimalarial activity of new diamine containing analogues [J].

Hindley, S ;

Ward, SA ;

Storr, RC ;

Searle, NL ;

Bray, PG ;

Park, BK ;

Davies, J ;

O'Neill, PM .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (05) :1052-1063

[10] New developments in synthetic peroxidic drugs as artemisinin mimics [J].

Jefford, Charles W. .

DRUG DISCOVERY TODAY, 2007, 12 (11-12) :487-495

← 1 2 3 →