Identification of β-Amino alcohol grafted 1,4,5 trisubstituted 1,2,3-triazoles as potent antimalarial agents

被引：33

作者：

Devender, Nalmala ^{[1
]}

Gunjan, Sarika ^{[2
,6
]}

Chhabra, Stuti ^{[3
]}

Singh, Kartikey ^{[1
]}

Pasam, Venkata Reddy ^{[1
]}

Shukla, Sanjeev K. ^{[4
]}

Sharma, Abhisheak ^{[5
]}

Jaiswal, Swati ^{[5
]}

Singh, Sunil Kumar ^{[2
]}

Kumar, Yogesh ^{[3
]}

Lal, Jawahar ^{[5
]}

Trivedi, Arun Kumar ^{[3
]}

Tripathi, Renu ^{[2
,6
]}

Tripathi, Rama Pati ^{[1
,6
]}

机构：

[1] Cent Drug Res Inst, CSIR, Med & Proc Chem Div, Lucknow 226031, Uttar Pradesh, India

[2] Cent Drug Res Inst, CSIR, Div Parasitol, Lucknow 226031, Uttar Pradesh, India

[3] Cent Drug Res Inst, CSIR, Div Biochem, Lucknow 226031, Uttar Pradesh, India

[4] Cent Drug Res Inst, CSIR, Sophisticated Analyt Instrument Facil Div, Lucknow 226031, Uttar Pradesh, India

[5] Cent Drug Res Inst, CSIR, Pharmacokinet & Metab Div, Lucknow 226031, Uttar Pradesh, India

[6] AcSIR, New Delhi 110001, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 109卷

关键词：

beta-aminoalcohol; Antiplasmodial; Antimalarial; Pharmacokinetics; p53 protein upregulation; INHIBITORS; SUPPRESSION; DISCOVERY; CHALCONES;

D O I：

10.1016/j.ejmech.2015.12.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a quest to discover new drugs, we have synthesized a series of novel beta-amino alcohol grafted 1,2,3-triazoles and screened them for their in vitro antiplasmodial and in vivo antimalarial activity. Among them, compounds 16 and 25 showed potent activity against chloroquine-sensitive (Pf3D7) strain with IC50 of 0.87 and 0.3 mu M respectively, while compounds 7 and 13 exhibited better activity in vitro than the reference drug against chloroquine-resistance strain (PfK1) with IC50 of 0.5 mu M each. Compound 25 showed 86.8% in vivo antimalarial efficacy with favorable pharmacokinetic parameters. Mechanistic studies divulged that potent compounds significantly boosted p53 protein levels to exhibit the antimalarial activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：187 / 198

页数：12

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