Title:Design, Synthesis and Molecular Docking Studies of Pyrazoline Derivatives
as PI3K Inhibitors
Volume: 27
Issue: 2
Author(s): Rohit Kumar, Arvind Kumar, Adarsh Kumar, Ankit Kumar Singh and Pradeep Kumar*
Affiliation:
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Ghudda, Bathinda,
151401, India
Keywords:
Cancer, PI3K, quinazoline, pyrazoline, naphthalene, in silico, molecular docking.
Abstract:
Aim: Design, synthesis and molecular docking studies of quinoline/naphthalene containing
pyrazoline derivatives as PI3K inhibitors.
Background: Phosphatidylinositol 3-kinases (PI3Ks) belong to the family of enzymes, which are
associated with various cellular functions such as cell growth, proliferation, differentiation etc.
Overexpression or any changes in these functions may result in various abnormalities, which in
turn cause cancer.
Objectives: To perform synthesis and molecular docking studies of quinoline/naphthalene containing
pyrazoline derivatives as PI3K inhibitors.
Methods: 2-Chloroquinoline-3-carbaldehyde was synthesized by a reaction of acetanilide and
POCl3. The latter was reacted with substituted acetophenones to synthesize chalcones, which were
reacted with substituted phenyl hydrazines to yield pyrazoline derivatives (Series I). Similarly, pchloro
benzaldehyde was reacted with 2-acetonapthone to yield chalcone with substituted phenyl
hydrazines to yield pyrazoline derivatives (Series II).
Results: The synthetic compounds were subjected to molecular modelling experiments using Schrodinger
2016 software and evaluated in silico for their PI3K binding affinities. All the compounds had better docking
scores than AMG-319 (-4.36 Kcal/mol) and comparable docking scores with PI-103 (-6.83 Kcal/mol).
Conclusion: Compounds 5 and 3 had the best docking scores (-7.85 and -7.17 Kcal/mol, respectively). The
synthesized compounds have better docking scores than the reference drug AMG-319. As a result, they
might be used as lead molecules in investigating PI3K inhibitors.
