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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

In silico Study and Solvent-free one-pot Synthesis of Tetrahydropyrimidine derivatives by Mechanochemistry Approach for Targeting Human Neutrophil Elastase against Lung Cancer

Author(s): Ashish Patel*, Karan Gandhi, Sweta Shah, Darshan Patel, Shreyas Chhatbar, Drashti Shah, Stuti Patel, Harnisha Patel and Tushar Bambharoliya

Volume 18, Issue 4, 2022

Published on: 16 September, 2022

Page: [293 - 306] Pages: 14

DOI: 10.2174/1573409918666220622232501

Price: $65

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.

Keywords: Biginelii condensation, mechanochemistry, human neutrophil elastase, tetrahydropyrimidine, lung cancer, green chemistry.

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