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Author Notes:

Corresponding author: D. Kalman, Emory University School of Medicine, 615 Michael Street, Whitehead Research Building #144, Atlanta, GA 30322, USA. dkalman@emory.edu.

We thank members of the Kalman Laboratory, R. Sonowal and G. Patel, for helpful discussions.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Chemistry, Medicinal
  • Pharmacology & Pharmacy
  • Curcumin
  • Curcumin analogs
  • Tuberculosis
  • Mycobacteria
  • MONO-CARBONYL ANALOGS
  • ANTIINFLAMMATORY AGENTS
  • ANTICANCER PROPERTIES
  • DRUG DESIGN
  • UBS109
  • DISCOVERY
  • PATHWAY
  • EF31

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

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Journal Title:

European Journal of Medicinal Chemistry

Volume:

Volume 92

Publisher:

, Pages 693-699

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2015 Published by Elsevier Masson SAS.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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