Chemical investigation of plant extracts for new antimicrobial agents.

摘要

Individuals with compromised immune systems suffer from infections caused by many different opportunistic bacterial and fungal pathogens. The multiple drug resistance of those pathogens makes them a threat to the general population because of the lack of effective therapies for infections that should otherwise present no great health risk. In this study, over one-thousand randomly selected plant extracts from the Open Repository of the National Cancer Institute were screened for antimicrobial activity against bacteria including Mycobacterium smegmatis, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and fungi including Candida albicans and Cryptococcus albidus . The screens were performed using a newly developed 96-well microplate assay. The most active and taxonomically unique extracts together with additional extracts from the same plants but different plant parts were further evaluated in secondary bioassays. Based on the positive results from the secondary screens, extracts from four plants in the Annonaceae, Dipterocarpaceae, and Rubiaceae families were selected for chemical investigation for novel antimicrobial agents and/or known antimicrobial agents with novel antimicrobial activities. Four known diterpenes, ent-trachyloban-19-oic acid ( 1), ent-kaur-16-en-19-oic acid (2), 8(14)15-pimaradien-18-oic acid (3), and 7,15-pimaradien-18-oic acid (4), were isolated from the stem bark extract of Mitrephora celebica (Annonaceae). Compounds 1 and 2 exhibited significant antimicrobial activity against MRSA and My. smegmatis. In addition, one novel polyacetylene carboxylic acid, 13(E),17-octadecadiene-9,11-diynoic acid (5), together with the known 17-octadecene-9,11,13-triynoic acid (6), were also isolated from the Mi. celebica stem bark extract. Both compounds exhibited significant activity against MRSA and My. smegmatis. Bioassay-guided fractionation of an ethyl acetate-soluble extract of the stem bark of Vatica oblongifolia (Dipterocarpaceae) led to the isolation of two novel resveratrol tetramers, hopeaphenol A (7) and isohopeaphenol A (8), and the known vaticaphenol A (9). Compounds 7 and 9 were moderately active against MRSA and My. smegmatis. Chemical investigation of the biologically active wood extract of Pentagonia sp. nov. (Rubiaceae) led to the isolation of the known 6-octadecynoic acid (10), which exhibited significant activity against Ca. albicans and My. smegmatis.