Molecular Docking, Pharmacokinetic, and DFT Calculation of Naproxen and its Degradants
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 9, Issue 5
Abstract
Most of the nonsteroidal anti-inflammation drugs (NSAID) have some demerits depending on type and nature of physical conditions and limit of doses. Herein, we report the optimization of Naproxen and its degradants employing density functional theory (DFT) with B3LYP/6-31g+(d,p) level theory to elucidate their thermal and molecular orbital properties. Molecular docking and nonbonding interactions have been performed against prostaglandin synthase protein (5F19) to search binding affinity and interactions of all compounds with the respective protein. Pharmacokinetic properties also calculated to search their absorption, metabolism, and carcinogenicity. Naproxen is a naphthalene nucleus bearing nonsteroidal an- ti-pyratic and anti-inflammatory drug, that plays key role against cyclooxygenase (COX) leading to suppress prostaglandins accumulation caused by various diseases [1,2]. It has undesirable side effects upon routine medication due to free form of terminal acid group. A bunch of modification focused on terminal acid group protection or prodrug derivatization in order to minimize the secondary effect [1-3]. Several degradative studies suggested to investigate the nature of degradant in the different chemical and physical environment [4,5]. In this study, we considered all the four impurities including degradants such as D1, D2, D3, and D4 with that parent Naproxen. Here D2 and D4 degradative products were obtained during acid hydrolysis (1N HCl at 60°C for 2hrs) and base hydrolysis (1N NaOH at 60°C for 6hrs) where as D1 and D3 were considered as metabolite and process related by products [4]. Previously, computational studies of Naproxen and some of its modified derivatives also reported [6,7] (Figure 1). In this investigation, we report the optimization and prostaglandin H2 (PGH2) inhibition pathway of Naproxen and its degradants utilizing molecular docking, nonbonding interactions, and pharmacokinetic calculations. Enthalpy, free energy, dipole moment, HOMO (highest occupied molecular orbital), LUMO (lowest unoccupied molecular orbital), hardness, softness, chemical potential has and chemical potential have been studied for every molecule. Molecular docking and nonbonding interactions calculation are performed to understand the binding affinity and binding mode(s) of all structures with the receptor protein (5F19). Some of the compounds show improved thermal, molecular orbital and binding properties (Figure 2).
Authors and Affiliations
Moniruzz aman, Mohammed Jabedul Hoque, Amrin Ahsan, Md Belayet Hossain
Keywords
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- EP ID EP586894
- DOI 10.26717/BJSTR.2018.09.001852
- Views 165
- Downloads 0
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