Identification of new dihydrophenanthrene derivatives as promising anti-SARS-CoV-2 drugs through in silico investigations

Abstract

To research, evaluate, and invent novel compounds that inhibit SARS-CoV-2 activity, a series of reported 39 substituted 9, 10-dihydrophenanthrene derivatives were subjected to a quantitative structure-activity relationship (QSAR) study. Gaussian 09 and ChemOffice programs were used to calculate the molecular descriptors employed to determine their impact on the studied activity. Then we reduced the number of descriptors by eliminating the redundant information using principal component analysis (PCA). The creation of molecular models was done by using multiple linear regression (MLR) according to the principles established by the Organization for Economic Co-operation and Development (OECD) and the validation by using external and internal validation, Y-randomization tests, and domain of applicability. Moreover, we evaluated the toxicity of developed compounds using ADMET and Molecular docking to determine their optimal position to form a stable complex. As a result, four molecules may be used to develop a novel drug that can inhibit SARS-CoV-2 without causing the side effect.

Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations

“…The designed compounds with a high value of pIC 50 against alpha-glucosidase activity were subjected to an ADMET analysis for the purpose of gaining insight into the pharmacological properties which includes several properties such as the absorption, distribution, metabolism, excretion, and toxicity [ 49 , 50 ]. The pkCSM website is widely used for predicting these properties and evaluating the behavior of compounds in the human body.…”

Structure‐Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates α‐Amylase Inhibitors

“…According to the Lipinski, Veber, Ghose, and Egan rules as mentioned in Table 2, we evaluate the oral availability of remaining compounds, and the results are listed in Table S2 and revealed that only 50 compounds successfully exceeded the mentioned filters with no violation in the following properties: molecular weight of less than 500 Da, hydrogen bond donor of fewer than 5 bonds, hydrogen bond acceptors, and rotatable bonds of less than 10 bonds, in addition to the molecular refractivity fewer than 130 Å, and total polar surface area of less than 140 Å. [49] The ADMET properties of the remaining compounds were also assessed using pKCSM and Swiss-ADME online tool and listed in Table S2, Table S3 and Table S4.…”

Identification of novel NLRP3 inhibitors: a comprehensive approach using 2D-QSAR, molecular docking, molecular dynamics simulation and drug-likeness evaluation

“…The molecular docking simulations were performed using the Autodock4 program (Trott and Olson 2009), which employs an empirical scoring function to evaluate the binding a nity between the receptor and ligands. The docking simulations provide insights into the potential binding modes and interactions between the ligands and the receptor (Abchir et al 2022;Yamari et al 2023). In summary, the material and methods of molecular docking involved the retrieval and optimization of the receptor structure, preparation of the receptor and ligands in the appropriate format, de nition of the binding site using a grid box, and the actual docking simulations performed with the Autodock4 program.…”