Chemical Descriptors, ADMET, Molecular Docking and Molecular Dynamics Simulation of Mannopyranoside Derivatives against Smallpox Virus Proteins
نویسندگان
1 Department of Applied Chemistry and Chemical Engineering, Faculty of Science, University of Chittagong, Chittagong, Bangladesh
2 Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, Bangladesh
3 Department of Pharmacology, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand, India
4 Gyani Inder Singh Institute of Professional Studies, Dehradun, Uttarakhand, India
5 School of Pharmacy & Research, Dev Bhoomi Uttarakhand University, Dehradun, Uttarakhand, India
6 Department of Pharmaceutical Chemistry, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand, India
7 Postgraduate School, Universitas Airlangga, Surabaya, Indonesia
8 Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, Bangladesh
9 Alpine Institute of Management and Technology, Dehradun, Uttarakhand, India
10 School of Pharmaceutics, Shri Guru Ram Rai University, Dehradun, Uttarakhand, India
11 Department of Pharmaceutical Chemistry, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand, India
doi
10.48309/ajca.2025.459071.1531چکیده
Employing computer-aided drug design techniques, the physicochemical, biological, and pharmacokinetic properties of several derivatives of methyl α-D-mannopyranoside were explored. Geometrical optimization was conducted using density functional theory (DFT) with a 3-21G basis set, yielding crucial insights into the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). From these data, softness, electron affinity, ionization potential, electronegativity, hardness, electrophilicity, and chemical potential were derived. Notably, compound 1 (mannopyranoside) exhibited the widest energy gap (0.27439 eV), while compound 4 (lauryl derivatives) displayed the narrowest energy gap (0.01924 eV). Furthermore, comprehensive studies encompassing geometrical, thermodynamic, molecular orbital, and electrostatic potential analyses were conducted to elucidate the physical and chemical behavior of the compounds. Molecular docking against the Smallpox virus (PDB 3IGC) proteins enabled the investigation of binding affinity, mode, and interactions with the receptor. ADMET prediction was employed to compare the absorption, distribution, metabolism, and toxicity of the compounds, revealing that compound 6 (a palmitoyl derivative) has the highest free energy and internal energy. A 100 ns molecular dynamics (MD) simulation was used to observe the complex structure formed by the 3IGC protein under in silico physiological conditions to determine its stability over time. It showed a stable conformation and binding pattern in a stimulating mannopyranoside derivative environment. Overall, this study provides valuable insights into the biochemical impact of these compounds on the environment and the human body, offering significant implications for future research endeavors. These findings suggest promising prospects for the development of effective antiviral agents targeting smallpox.
