Callyaerins, Cyclic Peptides from the Indonesian
Marine Sponge Callyspongia aerizusa with Potent and
Selective Antitubercular Activity
Georgios Daletos,1 Rainer Kalscheuer,2 Victor Wray,3 Peter Proksch1
1Institute
of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Universitaetsstrasse 1, 40225 Duesseldorf, Germany
2Institute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany
3Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany
Extraction and Isolation
The MeOH extract of Callyspongia aerizusa was
subjected to solvent-solvent partitioning to give nhexane, EtOAc and n-BuOH fractions. Column
chromatography of the EtOAc fractions, using
Sephadex LH-20 or silica 60M as stationary phase,
followed by purification with semi-preparative
reversed-phase HPLC afforded several callyaerin
derivatives.1,2
Basic structure of callyaerins
Ring
Callyaerin
R1
R2
R3
R4
R5
Sidechain
R6
R7
R8
C1
C2
C3
C4 C5
Phe Gly
A
IIe Hyp Val
IIe Leu Pro Pro
Leu
Pro
Ile
B
IIe Hyp
IIe Leu Pro Pro
Leu
Pro
Ile
C
His Hyp Leu Leu Pro Pro
Val
Pro
Leu
D
IIe
Phe Pro Hyp Pro Leu
Pro
Ile
Pro
IIe
IIe
Gly
Ile
Ile
IIe
Val
IIe
Phe Gly
Asn Ala IIe
E
Leu Pro Phe Phe Pro Pro
F
Val Pro Val Phe Pro
Pro
Leu
Phe
G
Leu Pro Pro Pro Pro Leu
Pro
Phe
Phe Phe
H
Val Pro Val Phe Pro Pro Leu
Pro
Ile
Hyp is γ-hydroxyproline
Anti-TB assay
All compounds were investigated in vitro against:
References
1.
Ibrahim, S. R. M.; Min, C. C.; Teuscher, F.; Ebel, R.; Kakoschke, C.;
Lin, W.; Wray, V.; Edrada-Ebel, R.; Proksch, P. Biorg. Med. Chem.
2010, 18, 4947-4956.
2.
Ibrahim, S. R. M.; Edrada-Ebel, R.; Mohamed, G. A.; Youssef, D. T.
A.; Wray, V.; Proksch, P. ARKIVOC 2008, (xii), 164-171.
- Mycobacterium tuberculosis
- THP-1 (human acute monocytic leukemia cell line)
- MRC-5 (human fetal lung fibroblast cell line)
Callyaerins showed moderate to strong activity towards
M. tuberculosis making these compounds interesting
candidates for further studies.
Conclusions
 The basic structural unit of the callyaerins comprises
a cyclic peptide with a linear peptide side chain, both of
variable size, linked through a non-proteinogenic (Z)2,3-diaminoacrylic acid (DAA) functional group.
 Callyaerins contain an unusually high number of
proline residues and hydrophobic amino acids (IIe, Leu
and Phe), which may contribute to the increased
biological activity of these peptides.
Acknowledgments
Financial support by BMBF (to P.P.) is gratefully acknowledged. This
work was supported by the Research Commission of the Medical
Faculty of the Heinrich-Heine-University Düsseldorf and by the
Jürgen Manchot Foundation (to R.K.). We wish to acknowledge Dr.
Nicole de Voogd (Leiden, Naturalis Biodiversity Center, Leiden, The
Netherlands) for identification of the sponges. We are indebted to
Mrs. C. Kakoschke (Helmholtz Centre for Infection Research,
Braunschweig, Germany) and Dr. R. Hartmann (Institute of Complex
Systems: Strukturbiochemie, Juelich, Germany) for recording NMR
spectra. We wish to thank Dr. Elisabeth Ferdinandus (University
Pattimura, Ambon) and Prof. Dr. Sumali Wiryowidagdo (University
Hassanudin, Makassar), both from Indonesia, for their support and
help during sponge collection.