Synthesis of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives and their biological evaluation

Article abstract of DOI:10.1016/j.bmcl.2015.11.063

A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60 °C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride to form the corresponding amine. The synthesized derivatives were further subjected to biological evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3, MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was observed that the carboxylated quinolone derivatives with hexanoic (8a), octanoic (8b), lauric (8d) and myristic (8e) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a) exhibited promising activity against both bacterial and fungal strains and significant antibacterial activity was observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9 μg/mL). The compound 8a also showed excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with MIC values of 2.1 and 4.6 μg/mL, respectively.

Full text of DOI:10.1016/j.bmcl.2015.11.063

Bioorganic & Medicinal Chemistry Letters 26 (2016) 613–617
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,
4-dihydro-4-oxoquinoline-3-carboxylate derivatives and their
biological evaluation
Vijayendar Venepally a,c, R. B. N. Prasad a,c, Y. Poornachandra b,c, C. Ganesh Kumar b,c
,
Ram Chandra Reddy Jala a,c,
⇑
a Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
b Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
c Academy of Scientific and Innovative Research, New Delhi, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A
series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate
Received 3 September 2015
Revised 30 October 2015
Accepted 19 November 2015
Available online 29 November 2015
derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain
the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at
60 °C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride
to form the corresponding amine. The synthesized derivatives were further subjected to biological
evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3,
MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was
observed that the carboxylated quinolone derivatives with hexanoic (8a), octanoic (8b), lauric (8d) and
myristic (8e) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results
also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a) exhibited
promising activity against both bacterial and fungal strains and significant antibacterial activity was
Keywords:
Cancer cell lines
Carboxylated quinolones
Lauric
Myristic
Cytotoxicity
Antimicrobial
Antioxidant
observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9
excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with
MIC values of 2.1 and 4.6 g/mL, respectively.
lg/mL). The compound 8a also showed
Hexanoic acid
l
Ó 2015 Elsevier Ltd. All rights reserved.
In the recent years, antimicrobial resistance has gained a
renewed interest from a clinical perspective and has raised a
serious public health attention due to the incidence of various
drug-resistant microbial infections. The primary reason for antimi-
crobial resistance is the wide usage or misuse of the currently
available antimicrobial agents by the medical practitioners.1,2 In
view of the increased threat from these drug-resistant Gram-posi-
tive and -negative bacterial strains and also Candida strains, there
is a continuous demand to identify new antimicrobial agents.
Quinolone as a privileged scaffold represents one of the most
important structural unit prevalent in various naturally occurring
and bioactive compounds. Quinolones are presently used as
antibacterial agents for the treatment of many systemic infections
and functionally exert their effect by inhibition of two type II
bacterial topoisomerases, namely DNA gyrase and topoisomerase
IV.3,4a,b In addition, Fluoroquinolones (FQs) belong to the class of
quinolone compounds with a broad spectrum of antibacterial
activity.5–7 FQs are presently used for the treatment of various bac-
terial infections of the respiratory, gastrointestinal and urinary
tract, as well as sexually transmitted diseases and chronic
osteomyelitis.8–11 In the recent years, non-classical anti-tumor
activity of FQ derivatives has been described.12–14
They also display anti-proliferative activity in some tumor
cells such as breast cancer cells,15 bladder transitional cell
carcinoma,16–18 non-small cell lung carcinoma,19 prostate
carcinoma20,21 and colorectal carcinoma.22 One of the quinolone
derivatives, ciprofloxacin (CP) displays anti-proliferative and apop-
tosis-inducing activities both on prostate and bladder cancer
cells.23,24,20,21 From a structure–activity relationship (SAR) per-
spective on different quinolone derivatives, it was noticed that dif-
ferent substituents (however, these substituents are not fatty acyl
moieties) at C-7 position of the FQ that contribute to their antimi-
crobial activities.25–27 Another study suggested that by increasing
the bulkiness of the C-7 substituent resulted in the enhancement
of antibacterial activities.28 Further, the side chains at the C-7
⇑
Corresponding author. Tel.: +91 40 27191838.
E-mail addresses: jrcreddy10@gmail.com, ram@iict.res.in (R.C.R. Jala).
http://dx.doi.org/10.1016/j.bmcl.2015.11.063
0960-894X/Ó 2015 Elsevier Ltd. All rights reserved.

614
V. Venepally et al. / Bioorg. Med. Chem. Lett. 26 (2016) 613–617
position of the quinolones may interact with the target enzyme.29–31
In addition, many fatty acids32 and fatty amides33 are known
to exhibit antimicrobial and cytotoxic activities. Long alkyl/alkenyl
chains exhibited antimicrobial activity and some fatty acid deriva-
tives were also known to possess antitumor and anti-depressant
activities.34–36 Some reports exist on the heterocyclic and fatty
acid-based hybrids exhibiting biological activities.37,38 However,
there is paucity of information on the synthesis and biological eval-
uation of carboxylated quinolone derivatives with C-7 fatty amide
substitution. Considering these facts, the present study was under-
taken to replace the C–N bond in quinolones with different fatty
amides and further evaluated their cytotoxicity, antioxidant and
antimicrobial activities.
The synthesis of target compounds (8a–h) is described in
Schemes 1 and 2. Carboxylated fatty amide quinolone derivatives
were obtained using a synthetic route comprising of 8 steps. The
starting material, 3,4-difluoro nitro benzene (1) was converted to
3,4-difluorobenzenamine (2) by a facile method in which iron
and ammonium chloride were taken in methanol and water at
RT and the contents were further refluxed at 90 °C. Then 3,4-diflu-
orobenzenamine (2) was treated with diethyl ethoxymethyl ene-
O
O
h
OH
R
Cl
R
10 (a-h)
9 (a-h)
R = - (CH2)4-CH3, - (CH2)6-CH3, - (CH2)8-CH=CH2,
- (CH2)10-CH3, - (CH2)12- CH3, - (CH2)14-CH3,
- (CH2)7-CH=CH2-(CH2)7-CH3, - (CH2)16- CH3.
Scheme 2. Synthesis of fatty acid chlorides. Reagents and conditions: (h) COCl2, cat.
DMF, DCM, 3 h.
amount of dimethyl formamide in dichloromethane at 0 °C for
3 h (Scheme 2). The fatty acyl chlorides so formed were treated
with compound 7 in the presence of triethyl amine in dichloro-
methane to form the corresponding target compounds (8a–h),
which were purified by column chromatography.
All the synthesized compounds (8c–h) were screened against a
panel of four cancer cell lines such as DU145, A549, SKOV3, MCF7
and IMR-90 (normal lung cell line) and Doxorubicin was used as a
standard positive control. The cytotoxicity results for all the syn-
thesized compounds are depicted in Table 1.
malonate
to
yield
diethyl
2-((3,4-difluorophenylamino)
Most of the compounds showed significant cytotoxic effect.
Among the tested compounds, the compounds 8a, 8b, 8d and 8e
exhibited promising cytotoxicity against all the cancer cell lines.
Further, these promising compounds were screened against IMR-
90 (Normal lung cell line). The selectivity index (SI) was also deter-
mined using the following formula: SI = IC50 of pure compound in a
normal cell line/IC50 of the same pure compound in cancer cell line,
where IC50 is the concentration required to inhibit 50% of the cell
population. High SI value (>2) of a compound gives a selective
toxicity towards cancer cells, while the compound with SI value
<2 is considered to give general toxicity in which it also can cause
cytotoxicity in normal cells.43 The compounds 8a, 8b, 8d and 8e
comprising of 6 (hexanoyl), 8 (octanoyl), 12 (dodecanoyl) and 14
(tetradecanoyl) carbon chain lengths, respectively, containing
amide linkage at the C-7 position exhibited promising cytotoxicity
against all the tested cancer cell lines. This observation corrobo-
rates with some of the earlier studies which suggests that
methylene)malonate (3). The compound 3 was thermally cyclized
at 255 °C for 6 h to give ethyl 6,7-difluoro-1,4-dihydro-4-
oxoquinoline-3-carboxylate (4) where the product was obtained
by filtration of the reaction mixture at room temperature.39
Ethyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (4)
was directly treated with iodoethane in the presence of potassium
carbonate at 85 °C to form ethyl-1-ethyl-6,7-difluoro-1,4-dihydro-
4-oxoquinoline-3-carboxylate (5).40
In this method the key step was the formation of azide at C-7
position selectively by the reaction of ethyl-1-ethyl-6,7-difluoro-
1,4-dihydro-4-oxoquinoline-3-carboxylate (5) with sodium azide
at 60 °C in dimethyl formamide to yield compound 6.41 The com-
pound 6 was subjected to a simple catalytic reduction in which
zinc and ammonium chloride mixture was used as catalyst to yield
compound 7.42 In all the above conversions, moderate to good
yields were obtained (33–77%).
On the other hand, fatty acids (10a–h) were converted to fatty
acid chlorides by oxalyl chloride in the presence of catalytic
x
-hydroxy fatty acid analogs and 2,6-diisopropylphenol fatty acid
O
O
F
F
F
F
F
F
F
F
O
O
O
b
c
a
O
NH
O
NH2
N
H
N
O
1
3
2
4
O
d
O
N
O
O
O
O
N
O
F
F
F
O
O
O
f
e
NH2
N3
F
N
6
7
5
O
N
O
F
O
O
g
NH
R
8(a-h)
R = - (CH2)4-CH3, - (CH2)6-CH3, - (CH2)8-CH=CH2,
- (CH2)10-CH3, - (CH2)12- CH3, - (CH2)14-CH3,
- (CH2)7-CH=CH2-(CH2)7-CH3, - (CH2)16- CH3.
Scheme 1. Synthesis of carboxylated fatty amide quinolones. Reagents and conditions: (a) Fe, NH4Cl, H2O, MeOH, 90 °C, 12 h; (b) diethyl ethoxymethyl enemalonate, 120 °C,
4 h; (c) diphenyl ether, 255 °C, 6 h; (d) K2CO3, C2H5-I, DMF, 85 °C, 16 h; (e) NaN3, DMF, 60 °C, 12 h; (f) Zn, NH4Cl, EtOH, H2O, 90 °C, 6 h; (g) acid chloride, triethyl amine, DCM,
RT, 12 h.

V. Venepally et al. / Bioorg. Med. Chem. Lett. 26 (2016) 613–617
615
Table 1
Cytotoxic activity of compounds (8a–h)
Test compounds
DU145
IC50 values in (
lM)
SIy
9.0
A549
SIy
9.9
SKOV3
SIy
MCF7
SIy
9.0
IMR-90
8a
9.8 0.22
8.9 0.26
9.2 0.32
66.5 0.38
10.3 0.16
9.6 0.11
24.3 0.15
—
8.6 0.34
8.1 0.28
91.2 0.58
9.8 0.14
8.2 0.16
17.8 0.24
—
10.2
11.2
9.8 0.11
7.9 0.14
64.6 0.55
11.2 0.11
9.1 0.22
18.6 0.25
—
88.2 0.6
91.2 0.12
—
79.8 0.18
86.4 0.28
—
—
8b
8c
8d
8e
8f
8g
10.1 0.18
87.3 0.52
12.1 0.12
10.4 0.14
25.2 0.28
—
9.0
9.9
11.5
6.6
8.3
7.7
9.0
8.1
10.5
7.1
9.4
8h
37.1 0.33
0.7 0.11
32.6 0.26
0.8 0.09
35.2 0.17
0.7 0.12
28.4 0.32
0.9 0.08
—
Doxorubicin (control)
30.4
26.6
30.4
23.6
21.3 0.32
y
Selectivity index (SI) = IC50 of pure compound in a normal cell line/IC50 of the same pure compound in cancer cell line, where IC50 is the concentration required to inhibit
50% of the cell population.
Table 2
The antimicrobial activities were examined against seven bac-
terial strains and one fungal strain and the results to this regard
are shown in Table 3. It was observed that among all the synthe-
sized compounds, hexanoic acid-based fatty amide carboxylated
quinolone derivative (8a) proved to be promising as it exhibited
antimicrobial activity against both bacterial and fungal strains.
Specifically the compound 8a showed good antimicrobial activity
against Bacillus subtilis MTCC 121, Staphylococcus aureus MTCC 96
and S. aureus MLS16 MTCC 2940 with MIC values of 7.8, 3.9 and
Antioxidant activity (DPPH radical scavenging activity) of compounds 8a–h
Test compound
EC50 (l
g mlꢀ1) (mean SD)
8a
8b
8c
8d
8e
8f
8g
8h
BHT
33.8 0.26
109.8 0.55
147.5 0.63
a
—
286.0 0.54
a
—
750.7 0.44
798.8 0.42
28.5 0.44
10.4 0.22
15.6
15.6
l
l
g/mL, respectively, and Escherichia coli MTCC 739 (MIC value
g/mL) as compared to other strains. While the other com-
a-Tocopherol
pounds showed MIC values of >125 lg/mL. From a structure–activ-
a
ity relationship perspective, it was observed that the basic
carboxylated quinolone scaffold has a substitution of different fatty
acids linked by amide coupling. The main structural difference
between 8a and other compounds is the chain length, that is, 8a
has a short chain length (hexanoyl moiety) as compared to other
analogs at the C-7 position. The minimum bactericidal concentra-
tion (MBC) of compound 8a was determined against four bacterial
strains and the results were compared with Ciprofloxacin as stan-
dard. The results to this regard are shown in Table 4. It was
observed that the compound 8a exhibited good MBC with MIC
No activity.
analogs were found to be excellent tumor growth inhibitors and
the cytotoxicity increased with a decrease in the chain length of
the fatty acid.44,45
On the other hand, compounds 8f and 8h showed moderate
cytotoxicity against all the tested cell lines (IC50 < 40 lM). Interest-
ingly, our results corroborate with the previous findings where
dodecanoyl and tetradecanoyl derivatives showed significant
in vitro cytotoxicity.46
value of 7.8 lg/mL against both Staphylococcus aureus MTCC 96
and Bacillus subtilis MTCC 121.
All the synthesized compounds (8a–h) were screened for DPPH
radical scavenging activity and the results to this regard are shown
in Table 2. It was observed that the compound 8a exhibited
promising antioxidant activity which was comparable to the stan-
dard, BHT, while the other tested derivatives showed moderate to
higher antioxidant activities.
Based on the results presented in Table 3, it was also interesting
to note that the compound 8a exhibited good antifungal activity
against Candida albicans MTCC 3017 (MIC value of 31.2 lg/mL) as
compared to other analogs. Considering this fact, the anti-fungal
activity study was extended to an additional 12 Candida strains
and Issatchenkia hanoiensis MTCC 4755.
Table 3
Antimicrobial activity of compounds 8a–h
Test compounds
Minimum inhibitory concentration (
lg/mL)
Micrococcus
luteus MTCC
2470
Staphylococcus
aureus MTCC 96 MLS-16 MTCC 2940
Staphylococcus aureus Bacillus
Escherichia
Pseudomonas
aeruginosa MTCC
2453
Klebsiella
planticola
MTCC 530
Candida
albicans MTCC
3017
subtilis MTCC coli MTCC
121
739
8a
8b
8c
8d
8e
8f
8g
8h
>125
>125
>125
>125
>125
>125
>125
>125
—
3.9
15.6
>125
>125
>125
>125
>125
>125
>125
—
7.8
15.6
>125
>125
>125
>125
>125
>125
>125
—
>125
>125
>125
>125
>125
>125
>125
>125
—
>125
>125
>125
>125
>125
>125
>125
>125
—
31.2
>125
>125
>125
>125
>125
>125
>125
7.8
>125
>125
>125
>125
>125
>125
>125
—
>125
>125
>125
>125
>125
>125
>125
—
Miconazole
(standard
control)
Ciprofloxacin
(standard
control)
0.9
0.9
0.9
0.9
0.9
0.9
0.9
—

616
V. Venepally et al. / Bioorg. Med. Chem. Lett. 26 (2016) 613–617
Table 4
Minimum bactericidal concentration (MBC) of compound 8a
Test compound
Minimum bactericidal concentration (lg/mL)
Bacillus subtilis
Staphylococcus aureus
S. aureus MLS16
Escherichia coli
MTCC 121
MTCC 96
MTCC 2940
MTCC 739
8a
7.8
1.9
7.8
0.9
31.2
0.9
31.2
0.9
Ciprofloxacin (standard control)
humans from a clinical perspective causing systematic infections
to life threatening systematic disorders.48
Table 5
Antifungal activity of compound 8a
Based on these facts, we screened the compound 8a against dif-
ferent Candida strains along with Issatchenkia hanoiensis MTCC
4755. The results to this regard are shown in Table 5.
It was observed that the compound 8a exhibited promising
antifungal activity against C. albicans MTCC 183 (MIC
Test organism
Minimum inhibitory
concentration ( g/mL)
l
8a
Miconazole
C. albicans MTCC 183
C. albicans MTCC 227
C. albicans MTCC 854
C. albicans MTCC 1637
C. albicans MTCC 3018
C. albicans MTCC 3958
C. albicans MTCC 4748
C. albicans MTCC 7315
C. parapsilosis MTCC 1744
C. aaseri MTCC 1962
15.6
62.5
31.2
31.2
62.5
31.2
31.2
31.2
31.2
31.2
31.2
62.5
31.2
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
7.8
value = 15.6
lg/mL), while the standard Miconazole showed an
MIC value of 7.8
lg/mL against all the tested fungal strains.
The minimum fungicidal concentration (MFC) was also deter-
mined for 8a against different Candida strains along with Issatchen-
kia hanoiensis MTCC 4755. The results were compared with
Miconazole as standard positive control. The results to this regard
are shown in Table 6.
C. glabrata MTCC 3019
C. krusei MTCC 3020
Issatchenkia hanoiensis MTCC 4755
Biofilms are structured communities comprising of many differ-
ent bacterial species having the ability to produce extracellular
polymeric substances (EPS) that adhere to biological and/or non-
biological surfaces. Biofilm formation is a survival strategy under
hostile environments that protects the microbes within the EPS
favouring growth, and enabling the cells to survive and dis-
perse.49,50 Biofilm infections are difficult to eradicate and cause
serious chronic infections to humans in both hospital and commu-
nity environments. They also exhibit increased antibiotic resis-
tance as well as resist phagocytosis and other components of the
body’s defense system.50 In medical environments, different bacte-
ria form biofilms through adhesion mechanism on several biomed-
ical implants such as stents, heart valves, prosthesis, vascular
grafts and urinary catheters.51 They cause problem in the clinics
contributing to huge health costs and mortality. It is reported that
12–25% patient mortality occurs due to catheter-related blood-
stream infections.52 In this context, the novel compounds that
can specifically target and inhibit the biofilm formation would be
of great significance as compared to the rational use of antibiotics
and/or biocides. Considering these facts, a systematic study was
undertaken to investigate whether the compound 8a exhibited a
specific anti-biofilm activity or whether this observation was sim-
ply related to a general toxic effect on the different Gram-positive
and Gram-negative bacterial strains. To this regard, the compound
8a was screened for anti-biofilm activity53 against Bacillus subtilis
MTCC 121, Staphylococcus aureus MTCC 96, Staphylococcus aureus
MLS16 MTCC 2940 and Escherichia coli MTCC 739 which are com-
mon and important nosocomial pathogens having the ability to
form biofilms. Based on the results shown in Table 7, it was
observed that hexanoic acid-based fatty amide carboxylated qui-
nolone derivative 8a showed excellent anti-biofilm activity against
Staphylococcus aureus MTCC 96 and Bacillus subtilis with MIC values
Table 6
Minimum fungicidal concentration (MFC) of compound 8a
Test organism
Minimum fungicidal
concentration ( g/mL)
l
8a
31.2
125
62.5
62.5
62.5
62.5
62.5
62.6
31.2
62.5
62.5
31.2
62.5
62.5
Miconazole
Candida albicans MTCC 183
C. albicans MTCC 227
C. albicans MTCC 854
7.8
15.6
15.6
15.6
7.8
7.8
15.6
7.8
7.8
7.8
7.8
15.6
7.8
C. albicans MTCC 1637
C. albicans MTCC 3017
C. albicans MTCC 3018
C. albicans MTCC 3958
C. albicans MTCC 4748
C. albicans MTCC 7315
C. parapsilosis MTCC 1744
C. aaseri MTCC 1962
C. glabrata MTCC 3019
C. krusei MTCC 3020
Issatchenkia hanoiensis MTCC 4755
7.8
Different Candida species identified as clinical pathogens cause
severe opportunistic nosocomial infections (candidiasis) among
immunologically compromised patients undergoing cancer
chemotherapy, immunosuppressive treatments, broad-spectrum
antibiotics and among HIV-infected individuals.47
Among the many pathogenic Candida strains, Candida albicans is
a dimorphic and predominant commensal fungal pathogen to
of 2.1 and 4.6 lg/mL, respectively.
Table 7
Biofilm inhibition activity of compound 8a
Test compound
IC50 values in (lg/mL)
Bacillus subtilis MTCC 121
Staphylococcus
S. aureus MLS16
Escherichia coli
aureus MTCC 96
MTCC 2940
MTCC 739
8a
4.6 0.28
0.7 0.09
2.1 0.12
0.6 0.06
9.8 0.36
0.4 0.11
8.7 0.42
0.5 0.08
Ciprofloxacin (standard control)

V. Venepally et al. / Bioorg. Med. Chem. Lett. 26 (2016) 613–617
11. Huang, E. S.; Stafford, R. S. Arch. Intern. Med. 2002, 162, 41.
617
The results clearly reveal that although not much information
about structure–activity relationship can be highlighted at this
stage, it was noticed that the compound 8a has a hexanoic acid
moiety attached to the basic carboxylated quinolone scaffold
exhibiting electron donating or electron withdrawing properties
which antagonize biofilm formation and probably may be con-
tributing to the anti-biofilm activity.
In conclusion, we have synthesized a series of novel C-7 linked
fatty amide derivatives of carboxylated quinolones through multi-
step synthesis with moderate to good yields. All the synthesized
compounds were evaluated for their cytotoxic, antioxidant and
antimicrobial activities. The quinolones with hexanoic (8a),
octanoic (8b), lauric (8d) and myristic (8e) fatty acid derivatives
exhibited promising cytotoxicity against all the cancer cell lines.
Among the tested derivatives, the hexanoic acid-based fatty amide
carboxylated quinolone derivative (8a) exhibited promising
antimicrobial, antifungal and biofilm inhibition activities. Further
studies are in progress to understand the mechanistic aspects of
the promising compounds. To the best of our knowledge, this the
first Letter on the synthesis and biological evaluation of C-7 linked
fatty amide derivatives of carboxylated quinolones.
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compound information) associated with this article can be found,
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