Antimicrobial activities of naphthazarins from Arnebia euchroma.
Bioassay-directed fractionation of extract of Arnebia euchroma led to the isolation of alkannin (1), shikonin (2), and their derivatives (3-8) as the active principles against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The stereochemistry of alpha-methylbutyryl alkannin (8) is revealed for the first time, and the antimicrobial activity of 8 was compared with its corresponding diastereomer (9). The derivatives 3-9 showed stronger anti-MRSA activity [minimum inhibitory concentrations (MICs) ranged from 1.56 to 3.13 microg/mL] than alkannin or shikonin (MIC = 6.25 microg/mL). Anti-MRSA activity of derivatives was bactericidal with minimum bactericidal concentration (MBC)/MIC < or = 2. In a time-kill assay, the bactericidal activity against MRSA was achieved as rapidly as 2 h. The derivatives 3-9 were also active against vancomycin-resistant Enterococcus faecium (F935) and vancomycin-resistant Enterococcus faecalis (CKU-17) with MICs similar to those with MRSA. Aromatic ester derivatives were also synthesized for antimicrobial activity comparison. None of these compounds were active against Gram-negative bacteria tested. Their cytotoxicity was also evaluated on selected cancer cell lines, and they expressed their activity in the range 0.6-5.4 microg/mL (CD(50)). Our results indicate that the ester derivatives of alkannin are potential candidates of anti-MRSA and anti-VRE agents with antitumor activity.
Shen
Chien-Chang
CC
National Research Institute of Chinese Medicine, Taipei 112, Taiwan.
Syu
Wan-Jr
WJ
Li
Shyh-Yuan
SY
Lin
Chia-Hung
CH
Lee
Gum-Hee
GH
Sun
Chang-Ming
CM
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D028082:Boraginaceae / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular; D002681:China; D004354:Drug Screening Assays, Antitumor; D004578:Electron Spin Resonance Spectroscopy; D013293:Enterococcus faecalis / Q000187:drug effects; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010051:Ovarian Neoplasms; D024301:Plant Bark / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; C018204:alkannin; C016101:shikonin; D014640:Vancomycin