Title:In-silico Studies, Synthesis, and Evaluation of Anti-inflammatory Activity
of Novel Pyrimidine Scaffold
Volume: 20
Issue: 10
Author(s): Ganesh Munde, Sunil Menghani*, Nilesh Rarokar, Deweshri Kerzare, Md. Asif Iqbal Chittur and Pramod Khedekar
Affiliation:
- Department of Pharmaceutical Chemistry, Krupanidhi College of Pharmacy, Bangalore- 560035, Karnataka,
India
Keywords:
Pyrimidine, perkin condensation, anti-inflammatory activity, molecular docking, COX-2, heterocyclic nucleus.
Abstract:
Background: The heterocyclic nucleus pyrimidine is present in several natural and synthetic
chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of
parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning,
and in turn, inflammatory reactions.
Objective: The objective of the present study is to evaluate some novel pyrimidine analogues for antiinflammatory
action.
Methods: Molecular docking studies of Indomethacin and selected analogues were carried out with the
COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidine-2-ol
derivatives was begun by following Perkin condensation between substituted acetanilides and substituted
aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment
with urea. All synthesized compounds were evaluated for in vivo and in vitro anti-inflammatory activity.
Results: The docking interaction reflects a good dock score when compared with indomethacin, a potent
Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding
while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in
good yield and confirmed by physical and spectral studies. In vitro studies showed that compounds 5a and
5e were better at controlling inflammation than the conventional treatment Antipyrine, while in vivo data
showed that compounds 5a, 5c, 5e, and 5h were better at controlling inflammation than the standard drug
Antipyrine.
Conclusion: The compound with more than one electron releasing group on the aniline moiety of pyrimidine
yields a decent result in the synthetic and experimental studies, but the absence of an electron withdrawing
group favours stronger anti-inflammatory activity on the target.
