Antibacterial properties of 5-substituted derivatives of rhodanine-3-carboxyalkyl acids
Med Chem Res
Antibacterial properties of 5-substituted derivatives of rhodanine- 3-carboxyalkyl acids
Waldemar Tejchman 0 1 2 3 4
● Izabela Korona-Glowniak 0 1 2 3 4
● Anna Malm 0 1 2 3 4
● Marek Zylewski 0 1 2 3 4
● Piotr Suder 0 1 2 3 4
0 Jagiellonian Center of Innovation, NMR Laboratory , Bobrzyńskiego 14, Kraków 30-348 , Poland
1 Department of Pharmaceutical Microbiology, Medical University of Lublin , Chodzki 1, Lublin 20-093 , Poland
2 Departament of Chemistry, Institute of Biology, Pedagogical University of Cracow , Podchorazych 2, Kraków 30-084 , Poland
3 Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology , Mickiewicza 30, Kraków 30-059 , Poland
4 Department of Biochemistry and Neurobiology, AGH University of Science and Technology , Mickiewicza 30, Kraków 30-059 , Poland
A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4′-(N,N-dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5 position were synthesised and their antibacterial activity was screened. All the rhodanine derivatives showed bacteriostatic or bactericidal activity to the reference gram-positive bacterial strains, but lack of activity to the reference Gramnegative bacterial strains and yeast strains was observed.
Rhodanine ● Thiazolidine-4-one ● Rhodanine-3- acetic acid ● Antibacterial activity
Introduction
The 2-thiazolidine-4-one derivatives traditionally named
rhodanine have been known for over 100 years, and due to
their fascinating properties they are still examined
(Lesyk
and Zimenkovsky 2004)
. These compounds have a broad
spectrum of biological effects (Jain et al. 2012). Rhodanine
derivatives show antimalarial
(Kumar et al. 2007)
,
antitubercular
(Alegaon et al. 2012)
, cytotoxic
(Chandrappa
et al. 2009)
, antitumor
(Rao et al. 2011; Lesyk et al. 2011)
,
antiviral (Kaminskyy 2015), and antibacterial activity
(Bhatti et al. 2013; Kavitha et al. 2006; Song et al. 2014)
.
The research to obtain new antibacterial compounds is
vitally important. Recently, due to excessive and improper
use of antibiotics, there has been an increasing rate of
antibiotic resistance in the bacterial strains
(Woodford
2003)
, thus new groups of compounds which may be useful
as antibacterial agents have been examined. A few reports
has been published regarding the rhodanine derivatives with
a carboxyalkyl acid moiety at the N-3 position
(Xu et al.
2012)
. Biological activity of hybrid compounds possessing
chalcone and rhodanine-3-acetic acid has been also studied
(Chen et al. 2010)
. Such hybrids demonstrated synergistic
effect. Antibacterial activity of rhodanine derivatives and
their oxygen analogues derived from 2,4-thiazolidinedione
was also compared
(Zvarec et al. 2012)
. However, the
results of present study suggested that rhodanine derivatives
showed greater antibacterial activity than their analogues
from the 2,4-thiazolidinedione group having at the C-2
position exocyclic oxygen atom. It was shown that the
activity of the rhodanine derivative correlates with the size
of the substituent at the C-5 position
(Pardasani et al. 2001)
.
The research conducted by
Miao et al. (2013)
and
Patel
et al. (2013)
indicated that antibacterial activity of the acid
derivatives occurred when a major hydrophobic group was
introduced to the arylidene substituent at the C-5 position.
The best results were achieved when an aryl group
additionally with an electron-withdrawing group was
introduced. The rhodanine derivatives possessing a
4-(N,Ndimethylamino)-benzylidene substituent at the C-5 position
were also examined. These compounds acted as β-lactamase
inhibitors
(Grant et al. 2000)
. Taking into account the data
presented by other authors, we decided to synthesise a series
of derivatives having carboxyalkyl (acetic, propionic,
butyric) acid fragment at N-3 position and benzylidene
para-substituent with dimethyloamino, diethylamino,
dibuthyloamino or diphenylamino group at C-5 position.
Chemistry
Our initial research proved that the antibacterial activity of
the rhodanine derivatives which have carboxyalkyl
fragment at N-3 position was more effective than the
compounds with a substituent containing an amino group at C-5
position. We synthesised a series of rhodanine derivatives
with a carboxyalkyl acid radical at N-3 position (acetic,
propionic, butyric, caproic). The synthesis of the
3carboxyalkylrhodanine acids (Scheme 1) was conducted
according to the modified procedure proposed by
Körner
(1908)
at the beginning of the 20th century.
The synthesised compounds underwent Knoevenagel
condensation with 4-diethylaminobenzoic, 4-dibutylaminobenzoic
aldehydes and 4-diphenylaminobenzoic aldehyde with
triethylamine as a catalyst. Quaternary ammonium salts, the
intermediates obtained during reactions, were not isolated but
transformed to appropriate acids with hydrochloric acid
(Scheme 2).
Material and methods
All reagents for the synthesis of rho (...truncated)