Potential anti-infective agents isolated from Artemisia pacifica Nutt and Guardiola platyphylla Gray (fam. Asteraceae).

Abstract

The dichloromethane extracts (1 mg/ml) of Artemisia pacifica Nutt and Guardiola platyphylla Gray (fam. Asteraceae) separately demonstrated in vitro growth inhibition of Staphylococcus aureus (UA 9-29), Bacillus subtilis (UA 2-27), Klebsiella pneumoniae (UA 3-9) and Candida albicans (UA 97). Each of these extracts were subjected to bioassay-directed solvent extraction and partition in order to obtain concentrated active fractions. Subsequently, the active compounds were isolated and identified from these fractions. Artemisia pacifica Nutt. The active compound was the major component isolated from A. pacifica. By comparing the physical and chemical data with previously reported data, this compound was identified as dehydrofalcarindiol. Dehydrofalcarindiol demonstrated growth inhibition against S. aureus (50 μg/ml), B. subtilis (25 μg/ml), K. pneumoniae (100 μg/ml) and C. albicans (25 μg/ml). Its diacetyl derivative was devoid of activity at 100 μg/ml. Guardiola platyphylla Gray. The active fraction obtained from G. platyphylla contained unstable compounds that decomposed in the presence of air. Size exclusion chromatography (Sephadex LH-20) was used to fractionate the active fraction. Two new sesquiterpenes, the o-catechol derivatives (1S,4S) and (1S,4R)-7,8-dihydroxy-11,12-dehydrocalamenene, were eluted from the column as a mixture. The mixture of their diacetyl derivatives was oxidized with CrO₃ in AcOH. The major oxidation product was identified as (1S)-7,8-diacetyl-4-oxodeisopropylcalamenene, thereby verifying the sole difference to be the configuration at C-4. This sesquiterpene mixture completely inhibited the growth of S. aureus (100 μg/ml), B. subtilis (50 μg/ml), K. pneumoniae (100 μg/ml) and C. albicans (100 μg/ml). After removal of the sesquiterpenes from the active fraction, the remaining compounds displayed the same level of activity. Another six compounds were also isolated from this mixture as acetylated derivatives due to their instability. Their dimeric structures were identified by 2D-NMR techniques (COSY, HETCOR and NOESY). These dimers may be artifacts since they were formed from their o-quinone monomers when kept at room temperature for a week or when heated at 60°C for 4 hours.