A virtual insight into mushroom secondary metabolites: 3D-QSAR, docking, pharmacophore-based analysis and molecular modeling to analyze their anti-breast cancer potential
Creators: name: Shafiq, Nusrat
name: Shakoor, Bushra
name: Yaqoob, Nazia
name: Parveen, Shagufta
name: Brogi, Simone
name: Salamatullah, Ahmad Mohammad
name: Rashid, Maryam
name: Bourhia, Mohammed
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Inorganic Chemistry
subject: FOS: Chemical sciences

description: Breast cancer is a major issue of investigation in drug discovery due to its rising frequency and global dominance. Plants are significant natural sources for the development of novel medications and therapies. Medicinal mushrooms have many biological response modifiers and are used for the treatment of many physical illnesses. In this research, a database of 89 macro-molecules with anti-breast cancer activity, which were previously isolated from the mushrooms in literature, has been selected for the three-dimensional quantitative structure–activity relationships (3D-QSAR) studies. The 3D-QSAR model was necessarily used in Pharmacopoeia virtual evaluation of the database to develop novel MCF-7 inhibitors. With the known potential targets of breast cancer, the docking studies were achieved. Using molecular dynamics simulations, the targets’ stability with the best-chosen natural product molecule was found. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity of three compounds, resulting after the docking study, were predicted. The compound <b>C1</b> (Pseudonocardian A) showed the features of effective compounds because it has bioavailability from different coral species and is toxicity-free for the prevention of many dermatological illnesses. <b>C1</b> is chemically active and possesses charge transfer inside the monomer, as seen by the band gaps of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) electrons. The reactivity descriptors ionization potential, electron affinity, chemical potential (μ), hardness (η), softness (S), electronegativity (χ), and electrophilicity index (ω) have been estimated using the energies of frontier molecular orbitals (HOMO–LUMO). Additionally, molecular electrostatic potential maps were created to show that the <b>C1</b> is reactive. Communicated by Ramaswamy H. Sarma The selected compounds from the mushroom were evaluated as potential breast cancer MCF-7 cell line inhibitor.Ligand-based 3D-QSAR study to analyze the structurally diverse compounds with experimentally reported IC<sub>50</sub>.Pharmacophore-based virtual screening of compounds.Molecular docking analysis pointed out the vital interaction of the hit with the protein’s amino acids.Absorption, distribution, metabolism, and excretion (ADME) and toxicity properties of the lead compounds were examined. The selected compounds from the mushroom were evaluated as potential breast cancer MCF-7 cell line inhibitor. Ligand-based 3D-QSAR study to analyze the structurally diverse compounds with experimentally reported IC<sub>50</sub>. Pharmacophore-based virtual screening of compounds. Molecular docking analysis pointed out the vital interaction of the hit with the protein’s amino acids. Absorption, distribution, metabolism, and excretion (ADME) and toxicity properties of the lead compounds were examined.