Abstract
Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional
medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial
activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts
exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 mg/mL using bioautography method, and
from 125 to 500 mg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline
alkaloids (1–3), and nine benzophenanthridine alkaloids (4–12) were isolated and the antimicrobial activity of the
benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest
spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory
concentrations of chelerythrine, of 1.50 mg/mL for all bacteria tested, and between 3.12 and 6.25 mg/mL for the yeast tested,
show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated
from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine
was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a
demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the
tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus
subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay,
suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of
chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced
oxidized protein products) levels when compared to the control group.