Title:In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine
derivatives by Mechanochemistry Approach for Targeting Human
Neutrophil Elastase against Lung Cancer
Volume: 18
Issue: 4
Author(s): Ashish Patel*, Karan Gandhi, Sweta Shah, Darshan Patel, Shreyas Chhatbar, Drashti Shah, Stuti Patel, Harnisha Patel and Tushar Bambharoliya
Affiliation:
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus,
Changa-388421, Anand, Gujarat, India
Keywords:
Biginelii condensation, mechanochemistry, human neutrophil elastase, tetrahydropyrimidine, lung cancer, green chemistry.
Abstract:
Background: Pyrimidine derivative has evinced its biological importance in targeting
lung cancer by inhibiting neutrophil elastase.
Methods: All THPM derivatives were synthesized by the grindstone method at ambient temperature
followed by molecular docking study for efficient binding interaction of THPM compounds by
targeting human neutrophil elastase (HNE) (PDB ID: 5A0A) and In-silico ADMET study using
PkCSM. Moreover, all synthesized compounds were characterized by spectroscopy techniques and
screened for anti-cancer activity using in vitro HNE assay kit.
Results: We reported a one-pot solvent-free mechanochemical approach for synthesizing tetrahydropyrimidine
(THPM) derivatives from various aromatic aldehydes, ethyl cyanoacetate, and urea
followed by in silico study and evaluation against human neutrophil elastase (HNE) for treatment of
lung cancer. We calibrated the best molecules that bound to specific targets more efficiently using a
molecular docking approach and provided the desired efficacy. In-silico ADMET studies revealed
that all best-scored compounds had drug-like characteristics for potential use as human neutrophil
elastase inhibitors (HNE) in lung cancer treatment. Additionally, the in vitro studies revealed that
compounds 1, 2, and 8 show potent HNE inhibitory activity for lung cancer treatment.
Conclusion: In a nutshell, the tetrahydropyrimidine (THPM) scaffold and its derivatives may serve
as potential HNE inhibitors for the development of a promising anti-cancer agent.