Microbial reactions on 7alpha-hydroxyfrullanolide and evaluation of biotransformed products for antibacterial activity.
7alpha-Hydroxyfrullanolide (1), a known sesquiterpenoid, was isolated from Sphaeranthus indicus using an antibacterial-activity-directed fractionation method. This compound had exhibited a significant antibacterial activity against Gram-positive bacteria. Chemical and microbial reactions were performed to prepare eight different analogues of compound 1 in order to evaluate these newly synthesized compounds for antibacterial activity. These compounds were 1beta,7alpha-dihydroxyfrullanolide (2), 7alpha-hydroxy-1-oxofrullanolide (3), 4,5-dihydro-7alpha-hydroxyfrullanolide (4), 11,13-dihydro-7alpha-hydroxyfrullanolide (5), 13-acetyl-7alpha-hydroxyfrullanolide (6), 2alpha,7alpha-dihydroxysphaerantholide (7), 4alpha,5alpha-epoxy-7alpha-hydroxyfrullanolide (8), and 4beta,5beta-epoxy-7alpha-hydroxyfrullanolide (9). Microbial reactions on 1 using whole-cell cultures of Cunninghamella echinulata and Curvularia lunata yielded compounds 2-4. Incubation of compound 1 with the liquid cultures of Apsergillus niger and Rhizopus circinans yielded metabolites 5-7, while 8 and 9 were prepared by carrying out an epoxidation reaction on 1 using meta-chloroperbenzoic acid (mCPBA). Structures of compounds 2-9 were elucidated with the aid of extensive NMR spectral studies. Compounds 2-4 were found to be new metabolites. Compounds 1-9 were evaluated for antibacterial activity and found to exhibit a wide range of bioactivities. Antibacterial-activity data of 1-9 suggested that the bioactivity of 1 is largely due to the presence of C4=C5, C11=C13, and a gamma-lactone moiety.
Ata
Athar
A
Department of Chemistry, The University of Winnipeg, 515 Portage Avenue, Winnipeg MB R3B2E9, Canada. a.ata@uwinnipeg.ca
Betteridge
Jordan
J
Schaub
Emmanuel
E
Kozera
Daniel J
DJ
Holloway
Paul
P
Samerasekera
Radhika
R
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001234:Aspergillus niger / Q000378:metabolism; D019659:Asteraceae / Q000737:chemistry; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D012233:Rhizopus / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
C546099:7alpha-hydroxyfrullanolide; D000900:Anti-Bacterial Agents; D012717:Sesquiterpenes; C007787:frullanolide