Molecular Investigations of Novel Pyrano[2,3-c]Pyrazole Congeners as Potential HCoV-229E Inhibitors: synthesis, Molecular Modeling, 3D QSAR, and ADMET Screening
Mohamed G. Abouelenein , Aliaa H. El-boghdady , Hadeer M. Ali , Mohamed A. Said
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引用次数: 0
Abstract
The ongoing global pandemic caused by viral pathogens like SARS-CoV-2 (COVID-19) underscores that viral transmission is not confined by geographical boundaries. Thus, the development of novel antiviral therapies is critical to mitigate this crisis. Pyranopyrazoles have gained significant attention in medicinal chemistry due to their bioactive properties. In this study, we present a new series of pyranopyrazoles and their annulated derivatives, which were assessed for antiviral activity using a validated QSAR model and tested for their inhibitory effects against the viral 3CLpro enzyme. The findings were corroborated by various in silico techniques, including molecular docking, molecular dynamics simulations, and DFT calculations. Additionally, ADME studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of the novel lead compound 2. These investigations identified a series of metabolically stable pyranopyrazoles and their annulated derivatives as effective inhibitors of the SARS-CoV-2 3CLpro enzyme, offering a promising therapeutic option for COVID-19. We believe that pyranopyrazoles warrant further evaluation and chemical optimization for potential use in COVID-19 treatment.
期刊介绍:
The purpose of Polycyclic Aromatic Compounds is to provide an international and interdisciplinary forum for all aspects of research related to polycyclic aromatic compounds (PAC). Topics range from fundamental research in chemistry (including synthetic and theoretical chemistry) and physics (including astrophysics), as well as thermodynamics, spectroscopy, analytical methods, and biology to applied studies in environmental science, biochemistry, toxicology, and industry. Polycyclic Aromatic Compounds has an outstanding Editorial Board and offers a rapid and efficient peer review process, as well as a flexible open access policy.