Publications by authors named "Jacobus J M Meyer"

3 Publications

  • Page 1 of 1

The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action.

J Biol Chem 2013 Feb 28;288(7):5149-56. Epub 2012 Dec 28.

Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, United Kingdom.

Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M112.419069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576119PMC
February 2013

Bioactive diterpenes from Orthosiphon labiatus and Salvia africana-lutea.

J Nat Prod 2007 Feb 27;70(2):293-5. Epub 2007 Jan 27.

Department of Chemistry of Medicinal Plants, National Research Center, El-Tahrir Street, Dokki, Cairo, Egypt.

The known (+)-trans-ozic acid (1) and two new labdane diterpenoids (2 and 3) have been isolated from an ethanol extract of Orthosiphon labiatus. The structures of 2 and 3 were established mainly by 1D and 2D NMR spectroscopic means. The ethanolic extract of Salvia africana-lutea afforded the known abietane diterpenoids carnosol (4), rosmadial (5), and carnosic acid (characterized as its derivative 6). Compounds 3 and 6 exhibited MICs of 157 and 28 microM, respectively, against Mycobacterium tuberculosis, while 2 and 6 showed cytotoxic activity with IC50 82 and 69 microM, respectively, against a breast (MCF-7) human cancer cell line.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/np0680376DOI Listing
February 2007

Antibacterial activity of naphthoquinones and triterpenoids from Euclea natalensis root bark.

J Nat Prod 2004 Nov;67(11):1936-8

Department of Botany, University of Pretoria, 0002 Pretoria, South Africa.

Phytochemical studies of an ethanolic extract of Euclea natalensis root bark afforded two new compounds, octahydroeuclein (1) and 20(29)-lupene-3 beta-isoferulate (2), in addition to three known compounds, shinanolone (3), lupeol, and betulin. The chemical structures of 1 and 2 were determined by spectroscopic means. Shinanolone (3) showed inhibitory activity against Gram-positive bacterial strains and a drug-sensitive strain of Mycobacterium tuberculosis at a concentration of 0.1 mg/mL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/np030465dDOI Listing
November 2004