Structure-activity relationship of benzophenanthridine alkaloids from Zanthoxylum rhoifolium having antimicrobial activity.
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 µg/mL using bioautography method, and from 125 to 500 µg/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 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/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.
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Luciana de C
Lde C
Tavares
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Graciane
G
Zanon
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Andréia D
AD
Weber
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Alexandre T
AT
Neto
Graduate Program in Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Clarice P
CP
Mostardeiro
Graduate Program in Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Ivana B M
IB
Da Cruz
Graduate Program in Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Raul M
RM
Oliveira
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Vinicius
V
Ilha
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Pharmacology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Ionara I
II
Dalcol
Center for Research in Natural Products (NPPN), Federal University of Santa Maria, Santa Maria, RS, Brazil.
Ademir F
AF
Morel
D000470:Alkaloids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D013329:Structure-Activity Relationship; D032106:Zanthoxylum
D000470:Alkaloids; D000890:Anti-Infective Agents; D010936:Plant Extracts