Antibacterial diterpenes from Calceolaria pinifolia.
Two new isopimaranes, 19-methylmalonyloxy-ent-isopimara-8(9),15-diene (5) and 19-malonyloxy-ent-isopimara-8(9),15-diene (6), were isolated using bioassay-guided fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the aerial part of Calceolaria pinifolia along with eight other diterpenes (1-4, 7-10) and two triterpenes (11, 12). All compounds were assayed against Staphylococcus aureus (SA), methicillin-resistant S. aureus (MRSA), Bacillus subtilis (BS), and Escherichia coli (EC). 4-Epi-dehydroabietinol (2) and ent-isopimara-9(11),15-diene-19-ol (8) were found to be active against MRSA with MIC values of 8 and 2 microgram/mL, respectively. Mechanistic studies of 8 in BS suggested rapid and nonspecific inhibition of uptake and incorporation of radiolabeled precursors into DNA, RNA, and protein consistent with membrane-damaging effects in bacteria. Compound 8 did not afford protection against an acute infection with SA in mice.
Woldemichael
Girma M
GM
Department of Pharmacology, Division of Medicinal Products, College of Pharmacy, University of Arizona, Tucson, Arizona 85721-0207, USA.
Wächter
Gerald
G
Singh
Maya P
MP
Maiese
William M
WM
Timmermann
Barbara N
BN
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001118:Argentina; D001412:Bacillus subtilis / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D028083:Scrophulariaceae / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004224:Diterpenes