Akhtar Muhammad Nadeem, Khan Saira, Siddique Farhan, Bibi Mehvish, Zareen Seema, Yasmin Arooma, Hassan Syda Saba
Department of Chemistry, Faculty of Science, Ghazi University, Dera Ghazi Khan 32200, Pakistan.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan.
Cent Nerv Syst Agents Med Chem. 2025 Aug 11. doi: 10.2174/0118715249350047250725120152.
Epilepsy is a chronic neurological disease that affects around 50 million people globally. To cure this disorder, different antiepileptic drugs have been studied via computational approaches.
Density functional theory (DFT) and time-dependent-density functional theory (TDDFT) are employed to investigate the optoelectronic, photodynamic, and structural properties of antiepileptic drugs (EP1-EP5). The B3LYP/6-311 G (d, p) was used for the computational simulations study. Further comparisons with reference drug phenobarbital (R) and (EP1-EP5) drugs, several geometrical variables, including frontier molecular orbitals (FMOs), excitation energy, hole-electron overlap, density of states, binding energy, molecular electrostatic potential, transition density matrix, and density of states were performed.
Compared to R with antiepileptic drugs AEDs (EP1-EP5) exhibited a bathochromic shift of the absorption spectrum, lower excitation energies, and comparable binding energies. The findings showed that the antiepileptic drugs had significantly lower HOMO-LUMO energy gaps (Eg = 1.89-1.98 eV), pointing to their higher charge-directing behavior from HOMO to LUMO. The EP5 molecule exhibited excellent HOMO (-7.17 eV), LUMO (-2.80 eV), lowest energy band gap (4.37 eV), and boosted DOS results, which strengthens the drug-protein interaction.
EP5 exhibited the enhanced performance due to the presence of the electron withdrawing group in the acceptor region, extended conjugation, and better charge transference could be the best drug efficiency. During molecular docking, the robust interactions in EP5 with the antiepileptic proteins (4EY7 and 7SK2) showed an excellent structural template among the designed drugs. Among them, EP5 has better structural properties as an antiepileptic drug for future drug discovery.
癫痫是一种慢性神经疾病，全球约有5000万人受其影响。为治愈这种疾病，已通过计算方法研究了不同的抗癫痫药物。
采用密度泛函理论（DFT）和含时密度泛函理论（TDDFT）研究抗癫痫药物（EP1 - EP5）的光电、光动力和结构性质。计算模拟研究使用B3LYP/6 - 311G(d, p)。进一步将其与参考药物苯巴比妥（R）以及（EP1 - EP5）药物进行比较，对几个几何变量进行了研究，包括前线分子轨道（FMOs）、激发能、空穴 - 电子重叠、态密度、结合能、分子静电势、跃迁密度矩阵和态密度。
与R相比，抗癫痫药物（AEDs，即EP1 - EP5）表现出吸收光谱的红移、较低的激发能和相当的结合能。研究结果表明，抗癫痫药物的最高占据分子轨道（HOMO） - 最低未占据分子轨道（LUMO）能隙显著更低（Eg = 1.89 - 1.98 eV），表明它们从HOMO到LUMO具有更高的电荷导向行为。EP5分子表现出优异的HOMO（-7.17 eV）、LUMO（-2.80 eV）、最低能带隙（4.37 eV）以及增强的态密度结果，这增强了药物 - 蛋白质相互作用。
由于受体区域存在吸电子基团、共轭扩展以及更好的电荷转移，EP5表现出增强的性能，可能是最佳药物效率。在分子对接过程中，EP5与抗癫痫蛋白（4EY7和7SK2）之间的强相互作用在设计的药物中显示出优异的结构模板。其中，EP5作为未来抗癫痫药物发现具有更好的结构性质。
