Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

被引：65

作者：

Baldwin, Patrick R. ^{[1
]}

Reeves, Analise Z. ^{[2
,3
]}

Powell, Kimberly R. ^{[4
]}

Napier, Ruth J. ^{[3
]}

Swimm, Alyson I. ^{[4
]}

Sun, Aiming ^{[1
]}

Giesler, Kyle ^{[1
]}

Bommarius, Bettina ^{[4
]}

Shinnick, Thomas M. ^{[2
]}

Snyder, James P. ^{[1
]}

Liotta, Dennis C. ^{[1
]}

Kalman, Daniel ^{[4
]}

机构：

[1] Emory Univ, Dept Chem, Atlanta, GA 30322 USA

[2] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA 30333 USA

[3] Emory Univ, Microbiol & Mol Genet Grad Program, Atlanta, GA 30322 USA

[4] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 92卷

关键词：

Curcumin; Curcumin analogs; Tuberculosis; Mycobacteria; MONO-CARBONYL ANALOGS; ANTICANCER; UBS109; DISCOVERY; PATHWAY; EF31;

D O I：

10.1016/j.ejmech.2015.01.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：693 / 699

页数：7

共 38 条

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