ayush dangwal

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.

A set of newer generation imidazolo-pyrimidine derivatives was designed, synthesized, and evaluated for in-vitro alpha amylase activity. The design of the molecules was fully depend upon the structural features of previously developed molecules, and then all the molecules were docked with 1OSE porcine alpha amylase enzyme which showed good docking interaction scores between (-9.2 and -10.2) kcal/mol compared to standard acarbose (-6.9 kcal/mol). The interacting residues of (F1-F6) and 1OSE showed similar amino acid lining as present in the active site. The synthetic procedure of the molecules (F1-F6) was divided into three parts such as synthesis of chalcone derivative using aromatic aldehyde and acetophenone, synthesis of phenyl linked oxazolone derivatives using aromatic aldehyde and hippuric acid, then finally merged both the final products of step 1 and step 2 in presence of glacial acetic acid to obtain the final series of molecules. All the molecules showed characteristic peaks in FTIR, 1H-NMR, and Mass spectrometry with sharp melting point and single peak in TLC plate. Then in vitro alpha amylase inhibition activity was performed which showed that all the molecules observed with good IC50 values than standard acarbose. The presence of hydroxyl and methoxy group showed good impact on biological activity. Finally the results postulated that F3 was the best molecule as in vitro alpha amylase inhibitor.