et al. Chemistry Central Journal (2018) 12:29
Synthesis, antimicrobial activity,
pharmacophore modeling and molecular
docking studies of new pyrazole-dimedone
, Abdullah M. Al‑Majid
, Bander M. Al‑Qahtany
, M. Ali
, Mohamed Teleb
Mohamed H. Al‑Agamy
, Sehrish Naz
and Zaheer Ul‑Haq
Background: Design and synthesis of pyrazole‑dimedone derivatives were described by one‑pot multicomponent
reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad
substrate scope under benign conditions mediated by diethylamine (NHEt
). The molecular structures of the synthe‑
sized compounds were assigned based on diﬀerent spectroscopic techniques (
C‑NMR, IR, MS, and CHN).
Results: The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus
ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method.
Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l
exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B.
subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L.
Conclusion: In‑silico predictions were utilized to investigate the structure activity relationship of all the newly syn‑
thesized antimicrobial compounds. In this regard, a ligand‑based pharmacophore model was developed highlighting
the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the
most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE dock‑
ing suite against few reported target proteins.
Keywords: Pyrazole, Dimedone, Antifungal activity, Antimicrobial activity, Structure activity relationship, Inhibition
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Department of Chemistry, Faculty of Science, King Saud University, P. O.
Box 2455, Riyadh 11451, Saudi Arabia
Full list of author information is available at the end of the article
Nosocomial infections caused by antibiotic-resistant
gram-positive bacteria have become a serious medical
problem with an alarming increasing rate worldwide.
Methicillin-resistant Staphylococcus aureus (MRSA),
vancomycin-resistant enterococci (VRE) and penicil
lin-resistant Streptococcus pneumoniae (PRSP) are of
particular concern among various hospital-acquired
infections . Accordingly, emerging investigations have
provided new insights into developing novel, safe and
eﬀective antibacterial agents. Within this scope, pyra
zole based antibacterial agents attracted great interest
. Generally, pyrazoles display innumerable pharma
cological activities ranging from analgesic, antipyretic,
antimicrobial, anti-inﬂammatory, anticancer eﬀects to
antidepressant, anticonvulsant, and selective enzyme
inhibitory activities [2–11]. Recently, Barakat et al, have
been reported novel pyrazole hybrid architectures as
eﬃcient antibacterial agents. Various pharmacophores
were linked to the pyrazole core to build bioactive scaf
folds [12, 13]. Within this approach, cyclic dicarbonyl