Amino Acids (2018) 50:479–485
Characterization of antimicrobial and hemolytic properties
of short synthetic cationic lipopeptides based on QSAR/QSTR
Katarzyna E. Greber
· Krzesimir Ciura
· Mariusz Belka
· Piotr Kawczak
· Joanna Nowakowska
· Tomasz Bączek
Received: 23 October 2017 / Accepted: 12 December 2017 / Published online: 20 December 2017
© The Author(s) 2017. This article is an open access publication
In this study, we investigated the inﬂuence of molecular descriptors of cationic lipopeptides on their antimicrobial activity and
hemolytic properties. The quantitative structure–activity relationship and quantitative structure–property relationship models
were constructed. The antimicrobial, hemolytic and retention data were used as dependent variable and structural parameters
as the independent ones. The obtained results suggest that the chromatographic indexes can be employed for prediction of
antibacterial activity and that lipopeptides present nonspeciﬁc interaction between erythrocytes and bacterial membranes.
Keywords QSAR · QSRR · Antimicrobial lipopeptides · MIC · Hemolysis
Development of new antimicrobial agents is of the most
important challenge these days. Antimicrobial peptides
and lipopeptides (AMPs), which reveal serious therapeutic
potential due to the broad spectrum of activity, rapid bacte-
rial killing, and synergy with classical antibiotics, are seen
to be very promising candidates. The antibacterial mode of
action of peptides and lipopeptides is associated mostly with
the interactions with bacterial bilayer (Colomb-Cotinat et al.
2016; Greber and Dawgul 2017).
Lipophilicity of compounds is well known as a vital
parameter in a quantitative structure–property relationship
(QSPR), quantitative structure–activity relationship (QSAR)
studies and quantitative structure–toxicity relationship
(QSTR). A particular example of QSPR is a quantitative
structure–retention relationship (QSRR) where the proper-
ties are deﬁned as chromatographic parameters. The QSRR/
QSAR approach was successfully applied to predict antimi-
crobial activities of others class of antibiotics (Ciura et al.
The main aim of this study was to investigate how
molecular descriptors inﬂuence the antimicrobial activity
and hemolytic properties of short cationic lipopeptides.
Additionally, QSRR models were built to evaluate the most
important descriptors that inﬂuence the chromatographically
determined lipophilicity of this class of chemicals.
Synthesis and purication
Lipopeptides were synthesized, purified and analyzed
according to the procedures described in details elsewhere
(Greber et al. 2017).
Handling Editor: M. S. Palma.
Katarzyna E. Greber and Krzesimir Ciura contributed equally to
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00726-017-2530-2) contains
supplementary material, which is available to authorized users.
* Katarzyna E. Greber
Department of Physical Chemistry, Faculty of Pharmacy,
Medical University of Gdańsk, Al. Gen. J. Hallera 107,
80-416 Gdańsk, Poland
Department of Pharmaceutical Chemistry, Faculty
of Pharmacy, Medical University of Gdańsk,
Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland