1. Conclusions
Introduction
Acknowledgements
Synthesis and Antimicrobial Studies of Pyrazole Derivatives as
Potent Anti-Methicillin-Resistant Staphylococcus aureus Agents
Hydrazone Derivatives
References
Synthesis
Future Directions
Results
Abstract
 Microbial resistance to antibiotics is a global
concern.
 Without urgent and coordinated action, the world
is moving toward a post-antibiotic era, in which
normal infections or minor injuries may become
fatal.
 In an effort to find new agents to combat this
resistance, we report the synthesis and
antimicrobial activities of new pyrazole
derivatives.
 No work up and no column purification
 10 g scale synthesis
 Easily available and inexpensive reagents
 Two dynamic functional groups for further
derivatization
Zone of Inhibition Testing
 Testing performed against multiple bacteria to
evaluate growth inhibition.
 Discs treated with 10 µL of 0.1 M compound
 Bacteria used: Staphylococcus aureus, Bacillus
subtilis, Pseudomonas aeruginosa, Enterobacter
aerogenes
This work was supported by College of Science and
Mathematics Arkansas State University, Jonesboro.
Arkansas Statewide MS facility, Grant Number P30
GM103450 from the National Institute of General
Medical Sciences of the National Institutes of
Health (NIH) for recording mass spectrometry. This
publication was made possible by the Arkansas
INBRE program, supported by grant funding from
the National Institutes of Health (NIH) National
Institute of General Medical Sciences (NIGMS)
(P20 GM103429).
HO
O
N
N
Ph
H
O
H
N
NH2R
N
Ph
N
N
O
HO
N
H
R
+
Reflux, 24 h
CH3OH
Derivative S. Aureus B. subtilis Derivative S. Aureus B. subtilis
1 7 7.5 6 12 12
2 No Activity No Activity 7 10 8.5
3 10 11.5 8 10 11.5
4 13 16.5 9 No Activity 7.5
5 17.5 18 10 No Activity 8.5
C+ 26 29 C- No Activity No Activity
 Values reported in millimeters
 Values are averages of two trials with deviations < 4mm
 Molecules showed no inhibition to Gram-negative bacteria
 C+ = Chloramphenicol (30 µg)
Figure 2: Synthesis of pyrazole base compound
Figure 4: Synthesis of hydrazone derivatives
Figure 3: 1H NMR spectrum of pyrazole base compound
Kucukguzel, S. G.; Senkardes, S. Eur. J. Med.
Chem. 2015, 97, 786-815.
Further testing will be performed to determine
the minimum inhibitory concentration (MIC) of the
active molecules. These results will indicate if
further attention is warranted. Additional
derivatives are also being synthesized to expand our
library of new molecules.
N
N
NH
N
NH2
O
Cl
Cl
F
Ruxolitinib (Treats intermediate or
high-risk myelofibrosis)
Crizotinib (Treats non-small
cell lung cancer)
N
N
CN
N
N
NH
N
N
F3C
S NH2
O
O
CH3
Celecoxib (nonsteroidal
anti-inflammatory drug)
Figure 1: Pyrazole derived drugs
 Many pyrazole derivatives have been approved
as drugs to treat various kinds of diseases.1
 Using efficient synthesis methods, we have
synthesized ten pyrazole derivatives to test
against various bacteria.
 The ten new molecules were tested against both
Gram-positive and Gram-negative bacteria.
 All molecules, with the exception of derivatives
2, 9, and 10, showed inhibition to both S. aureus
and B. subtilis, both Gram-positive bacteria.
 Zone averages as large as 17.5 mm for S. aureus
and 18.0 mm for B. subtilis were seen.
 No inhibition was noted against Gram-negative
bacteria.
Figure 5: Zone of inhibition results
Trent Rowe, Devin Allison, Evan Delaney, Adam Gottsponer, Danielle Gibler, Michael Branscum, David Gilmore, Allyn Ontko, Mohammad A Alam*
Department of Chemistry and Physics, and the Department of Biological Sciences, Arkansas State University, PO Box 409, State University, AR 72467
N
OH
O
NH2
H
acetophenone
AcOH, 24 h
N
OH
O
N
H Ph
N
N
O
H
O
OH PhPOCl3, DMF
0 to 70 °C, 5h
N
Ph
N
N
O
HO
NH2
N
Ph
N
N
O
HO
N
H
N
Ph
N
N
O
HO
N
H
F
N
Ph
N
N
O
HO
N
H
Br
N
Ph
N
N
O
HO
N
H
COOH
N
Ph
N
N
O
HO
N
N
CH3
N
Ph
N
N
O
HO
N
H
F
N
Ph
N
N
O
HO
N
H
Cl
N
Ph
N
N
O
HO
N
H
Cl Cl
N
Ph
N
N
O
HO
N
H
NO2
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.