In Silico Pharmacodynamics, Antineoplastic Activity and Molecular Docking of two Phytochemicals Isolated from Thymelaea microphylla

The lead compounds isolated from medicinal plants constitute a matrix for research and discovery of new drugs using in silico study and molecular docking. This work explores the in silico study and the molecular docking of two rare phytochemicals, namely Microphynolide A (1) and Microphynolide B (2), isolated from the Saharan medicinal plant Thymelaea microphylla (Thymelaeaceae family). In the current work, several integrated web-based in silico pharmacokinetic tools were used to estimate the druggability of two isolated phytochemicals. In addition, molecular docking was conducted using AutoDockVina 4.2 to study the binding interactions with the targets predicted employing the PharmMapper server. The toxicological study was evaluated using ProTox-II online server. DFT methods were utilized to evaluate some physicochemical properties of structures, vibrational wavenumbers, and molecular electrostatic potentials. Molecules (1) and (2) showed good ADMET profiles and antineoplastic activity. Also, they exhibited non-toxicity and belong to the Toxicity class VI (LD50 >8000 mg/kg) with immunotoxic activity. A good correlation was observed between the experimental and theoretical IR spectra, with no negative values in the theoretical spectra indicating the high stability of these compounds. Docking simulation studies against protein receptors Sulfotransferase 1A1 (PDB ID: 1LS6) and Angiogenin (PDB ID: 1B1I) displayed good binding affinity values of -5.8 and -6.8 kcal/mol, respectively, with number of H-bonding interactions. Furthermore, the control molecules p-Nitrophenol (pNP), Dopamine, Axitinib and Bevacizumab displayed values of binding energies of -6.7, -6.7, -6.9 and -6.3 Kcal/mol, respectively. This study provides evidence supporting that the two molecules could be effective drugs to inhibit cancer cells and did not show any acute toxicity or mutagenic effects.