Title:Design, Synthesis, and in vitro Evaluation of Derivatives of Quinoxaline-2-
One as a Myeloperoxidase Modulator Using in silico Methods
Volume: 20
Issue: 8
Author(s): Dakshinesh Parameswaran, Saravanan Thangavelu, Jubie Selvaraj, Selvinthanuja Chellappa, Lalitha Vivekanandan, Ravichandran Veerasamy and Prabha Thangavelu*
Affiliation:
- Department of Pharmaceutical Chemistry, Nandha College of Pharmacy, Affiliated with The Tamil Nadu Dr. MGR
Medical University-Chennai, Erode, 638052, Tamil Nadu, India
Keywords:
Quinoxaline-2-one derivatives, myeloperoxidase, antioxidant, anti-inflammatory, in silico docking, ADMET study.
Abstract:
Background: In some pathological situations, the overproduction of oxidising agents
also results in oxidative damage to host cell proteins and DNA, which induces abnormal expression
of inflammatory cytokines and chemokines. A recently discovered biomarker of inflammation
is myeloperoxidase. Various inflammatory conditions cause the release of this enzyme into
the extracellular environment.
Objective: Our study aimed to design, synthesize, and
in vitro evaluate derivatives of quinoxaline-
2-one as a myeloperoxidase modulator using
in silico methods.
Methods: A series of quinoxaline-2-one derivatives was synthesized and characterized by
various analytical techniques. Further, to confirm and explore the molecular mechanism,
an in silico docking study against the myeloperoxidase enzyme was performed (PDB ID:
1DNU).
Results: The compounds Q1, Q2, and Q5 showed better antioxidant activity in the DPPH assay,
whereas the nitric oxide scavenging assay showed the compounds Q2, Q4, and Q5 had significant
activity when compared to the standard IC
50 value (28.8 μg/ml). Besides, the anti-inflammatory
studies showed the compounds Q1, Q3, and Q5 had better inhibition (89.79%) when compared to
the standard drug aceclofenac (85.37%) at 1000 μg/ml concentration. The top three ligands for
myeloperoxidase (PDB ID: 1DNU) with the highest scores in activity were found as Q2, Q1, and
Q5, with scores of -13.2838, -12.5841, and -11.6906 Kcal/mol, respectively. The compounds
were efficiently bound to the myeloperoxidase active site with arene-arene, arene-cation, and
hydrogen bonding interactions.
Conclusion: By introducing the various heterocyclic rings and deactivating and activating
groups, we may produce a newer class of candidates for many infectious diseases. Thus, from the
computational studies carried out, we may obtain hints for optimising the molecular selectivity of
the quinoxaline-2-one derivatives to provide help in the design of new compounds for effective
myeloperoxidase enzyme modulators. However, further pharmacokinetics, pharmacodynamics,
preclinical, and clinical studies permit the design of the new agents without undesirable interactions.
