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

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.

2,2′-Fluorine mono-carbonyl curcumin induce reactive oxygen species-Mediated apoptosis in Human lung cancer NCI-H460 cells

“…It has been show spectral physiological and pharmacological activity including antiinflammatory (Fu et al, 2008), antibacterial (Baldwin et al, 2015), antioxidant (Gazal et al, 2014) and anticancer activity (Chen et al, 2016). Of particular interest is the anticancer property of curcumin, which has been the focus of hundreds of publications including several comprehensive reviews (Červinková et al, 2009;Ravindran et al, 2009;López-Lázaro, 2008;Reuter et al, 2008;Kunnumakkara et al, 2008).…”

Anti-Mycobacterial Activity of Capparis Spinosa L. Extract Against Clinical Isolates of Mycobacterium Tuberculosis

“…At Atlanta University, Baldwin et al (2015) [18] carried out a disk diffusion method and liquid measuring on laboratory samples and resistant strain to rifampin. The synergistic effect was confirmed with rifampin.…”

Ethnopharmacological Review of Natural Products in Cancer Prevention and Therapy

“…For centuries, this naturally occurring phytochemical is used in a number of pharmaceutical applications [84]. Novel investigations divulge that curcumin and also the curcumin derivatives have diverse pharmacological activities including anti-inflammatory [85], antiviral [86], antimicrobial [87], free radical scavenging activity [88], and anticancer activity [89].…”