1. Under the sea: An unusual antibiotic iodinated compound
Christine Jasmin*, Serge Lavoie*, David Brumley‡, and Julia Kubanek‡,*
*School of Biological Sciences, ‡ School of Chemistry and Biochemistry, Aquatic Chemical Ecology Center, Georgia Institute of Technology,
Atlanta, 30332
• In 70-95% of developing countries, traditional medicines are
still used for primary care.1
• Bacteria are developing more antibiotic resistance and as a
result pose a threat to humans.2
• Marine plant products provide a particular interest, due to the
plethora of biodiversity available.
• Marine natural products provide a varied source of
halogenated metabolites, particularly in marine macro- and
microalgae.3
• Through the investigation of a species of Fijian red algae,
Callophycus serratus, the bioactive compound,
diiodocallophycoic acid was found.4
• Scale up the isolation of diiodocallophycoic acid
• Investigate its possible activity against microbes such as
methicillin-resistant Staphylococcus aureus (MRSA)
• Finalize the stereochemical characterization of the compound.
Methods and Materials
Results
Name
Antibacterial MIC
(μg/mL)
MRSA VREF
Bromophycoic acid A 1.6 6.3
Bromophycoic acid B 25 >50
Bromophycoic acid C 6.3 >50
Bromophycoic acid D 12.5 >50
Bromophycoic acid E 6.3 1.6
Bromophycolide A 3.9 3.9
Bromophycolide B 3.9 2.0
Callophycoic acid G 1.6 3.1
Callophycoic acid A >50 0.8
Diiodocallophycoic acid 0.6 NT
1. Robinson, M. M.; Zhang, X.WHO 2011.
2. Levy, S.B.; Marshall, B. Nat. Med. 2004, 10, S122-S129.
3. Kladi, M.; Vagias, C.; Vassilios, R. Phytochem. Rev. 2004,
3, 337-366.
4. Brumley, D. Fijian Macroalgae: A continued source of
novel natural products, 2014.
5. Teasdale, M. E.; Shearer, T. L.; Engel, S.; Alexander, T. S.;
Fairchild, C. R.; Prudhomme, J.; Torres, M.; Le Roch, K.;
Aalbersberg, W.; Hay, M. E.; Kubanek, J. J. Org. Chem.
2012, 77 (18), 8000–8006.
Acknowledgements
The Kubanek Lab
• Ms. Kristy Syhapanha
The ACE REU Program
• Dr. Frank Stewart
• Dr. Brian Hammer
• Dr. Linda Green
• Dr. Claire Dell
Introduction
Conclusions
References
Diiodocallophycoic Acid’s Bioactivity
*NT= Not tested
The algae, collection G-0807 from Vitu Levi, Fiji, was extracted in methanol
and dichloromethane.5 Through serial fractionations, guided by liquid
chromatography mass spectrometry (LCMS) and nuclear magnetic resonance
spectroscopy (NMR), the compound (1), was isolated and purified. Using the
pure compound, a bioassay was performed against MRSA.
Through 2D NMR analysis techniques used to determine the interactions
between different atoms on the compound, the structure of 1 was determined.
Using this backbone, along with information from circular dichroism and
polarimetry, the 3D structure of the compound was finalized.
• While being structurally similar to previously
discovered callophycoic acids, diiodocallophycoic
acid uniquely contains iodine atoms
• Diiodocallophycoic acid is a potent antibiotic
against MRSA
• Discovery of diiodocallophycoic adds to the
wealth of knowledge of compounds derived from
natural products with medicinal properties
• High resolution mass of the deprotonated molecular ion was 816.888 g.
• Compound (1) showed an optical rotation of -56°(c=0.082 in CHCl3).
• Known compounds (2-4) were also isolated
Extraction
Methanol and
Methanol:Dichlo
-romethane 1:1
Liquid-Liquid
partition
Methanol/H2O,
Hexanes and
Dichloromethane
Solid Phase
Extraction
High Performance
Liquid Chromatography
0%
50%
100%
50 500 5000
MRSASurvival
Concentration (ng/ml)
0
100
200
300
400
500
600
700
800
900
1000
Relativeconcentrationof1
Fractions
LCMS guides future fractionation Hexane
DCM
MeOH/H O
50%
75%
80%
85%
90%
95%
100%
Solid Phase
Extraction
% Methanol
International Cooperative
Biodiversity Groups
Other Compounds Isolated Alongside 1
Objective
Chemical Shifts (ppm)
2
Liquid-
Liquid
Partition
NMR verifies purity and provides structural insight
1 is the most potent against MRSA in comparison
to other compounds isolated from this genus
Dose Response Curve shows a minimum inhibitory
concentration of 0.6 µg/mL against MRSA