Phenytoin from antiepileptic to covid-19: Synthesis, crystal structure, DFT, HSA, MEP and green biological study of phenytoin derivative as potential covid-19 drug candidates

Abstract

That's an interesting point! Phenytoin's potential in reducing cognitive deficits during COVID-19 is indeed intriguing. Its established status as an approved antiepileptic medication could lend credibility to exploring its effects on cognitive function in COVID-19 patients. This dual functionality could provide a unique angle for research and potential therapeutic interventions. This study reports the synthesis, characterization and importance of a new phenytoin derivative PD, C23H24N4O5. A biological molecular modelling study using a computer-aided tool, which is a clean technique of PD compared to the approved Phenytoin anti-COVID-19 drugs, was achieved. Docking the three compounds into 7JQ0 of COVID-19 Mpro showed the potential capability of PD compared to Phenytoin and the inhibitor. Binding affinity, for example, was -7.3, -6.9 and -6.6 kcal/mol, respectively. Noticeably, PD interacted with 75 % of the essential functional Mpro amino acids, such as G143 and H164, M49, C145, M165 and E166, comparable to the standards used. Further interesting findings that predicted compound toxicity and drug-likeness also found that PD was less toxic and bio-available as a drug than Phenytoin and the inhibitor. Superposition of our ligand PD against Phenytoin and the Inhibitor docked into7JQ0 using the same parameters showed similar interactions in the amino acid cavity, enhancing the possibility of PD being an anti-COVID-19 drug. The free computer-aided methods were used to significantly speed up the initial stages of drug discovery by narrowing down potential candidates for further laboratory testing.This compound adopts an L-shaped conformation. The lone pairs on the ring nitrogen atoms participate in π bonding in the ring. In the crystal, a layer structure was generated by NH···N, NH···O and CH···O hydrogen bonds plus CH···π(ring) interactions. Theoretical studies of the compound were calculated using the density functional theory (DFT) method with a B3LYP 6–311++G(d,p) basis set. The geometrical parameters after optimization were compared with the experimental values. Molecular Electrostatic Potential (MEP) and Hirshfeld Surface Analysis (HSA) were studied to investigate intermolecular interactions. Frontier Molecular Orbitals (FMOs), which were Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), were created, and the energy gap between these orbitals was calculated to understand the chemical stability of the molecule.