当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > An efficient synthetic route for preparation of antimycobacterial wollamides and evaluation of their in vitro and in vivo efficacy.

An efficient synthetic route for preparation of antimycobacterial wollamides and evaluation of their in vitro and in vivo efficacy.

Abstract：

:A convenient solid phase peptide synthetic (SPPS) route is reported for the preparation of antimycobacterial wollamides. The method is based on on-resin head-to-tail cyclization and is fast, efficient and amenable to automation. The in vitro antimycobacterial activities of the newly synthesized wollamides were evaluated against M. tuberculosis H37Rv (Mtb H37Rv). To assess their drug-likeness, in vitro pharmacokinetic (ADME) profiling was also performed. For wollamides with potent extracellular potency, intracellular activities and in vivo efficacy were determined. The results disclose the potent antimycobacterial (MICMtb H37Rv = 1.1 µM) and suitable drug-like properties of wollamide A (4b). Out of the synthesized wollamides, four compounds (4b-e) exhibited potent intracellular activities against Mtb H37Rv infected human macrophages (IC50 = 0.2-1.3 µM). Results of in vivo blood exposure and efficacy assays for 4d and 4e are discussed.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Asfaw H,Wetzlar T,Martinez-Martinez MS,Imming P

doi

10.1016/j.bmcl.2018.07.021

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

2899-2905

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30584-5

journal_volume

28

pub_type

杂志文章

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