Molecular docking and DFT study of antiproliferative ribofuranose nucleoside derivatives targeting EGFR and VEGFR2in cancer cells.

Antimetabolites are the most effective chemotherapeutics for treating cancer. They have exerted their anticancer effects by interfering with DNA synthesis. Recently, interest in modified nucleoside analogues has grown due to their superior efficiency. Nucleoside analogue derivatives have emerged as crucial candidates for cancer treatment due to their ability to target the cells responsible for cancer within the body specifically. The ability of nucleoside analogues derivatives to target specific molecular pathways has reduced toxicity and increased efficiency compared to traditional chemotherapy drugs. Nucleoside analogues have interfered with physiological nucleosides and induced cytotoxicity in cancerous cells. In this investigation, derivatives of ribofuranose nucleoside analogues have been designed. Density functional theory (DFT) calculations have been performed at the B3LYP/6-311 G(d,p) level. The designed molecules have been characterized by UV/Vis spectroscopy using the CPCM model in DMSO solvent, and molecular structural parameters, such as HOMO/LUMO and MEPS, have been determined. Derivative d1m has exhibited a high energy gap and low absorption energy compared to the other derivatives. Molecular docking of the designed molecules (d1o-d2m) has been performed with the EGFR and VEGFR2 proteins. d2o has shown good binding energy with the EGFR protein, while d1o has shown good results with VEGFR2. Global chemical parameters and NBO analysis have been conducted to investigate the derivatives charge transfer properties and chemical reactivity. NBO analysis has provided information about the donor and acceptor parts within a molecule, while global chemical parameters have given insights into the reactivity, stability, and solubility of the molecules. It has been found that the derivatives are more chemically reactive, thermodynamically stable, and have better binding affinity than the parent molecule. Based on the analysis, the drug interaction with the cancer-causing protein makes it more effective for cancer treatment.

Organic Molecular Glues to Design Three-Dimensional Cubic Nano-assemblies of Magnetic Nanoparticles.

Self-assembled magnetic nanoparticles offer next-generation materials that allow harnessing of their physicochemical properties for many applications. However, how three-dimensional nanoassemblies of magnetic nanoparticles can be synthesized in one-pot synthesis without excessive postsynthesis processes is still a bottleneck. Here, we propose a panel of small organic molecules that glue nanoparticle crystallites during the growth of particles to form large nanoassembled nanoparticles (NANs). We find that both carbonyl and carboxyl functional groups, presenting in benzaldehyde and benzoic acid, respectively, are needed to anchor with metal ions, while aromatic rings are needed to create NANs through π-π stacking. When benzyl alcohol, lacking carbonyl and carboxyl groups, is employed, no NANs are formed. NANs formed by benzoic acid reveal a unique combination of high magnetization and coercivity, whereas NANs formed by benzaldehyde show the largest exchange bias reported in nanoparticles. Surprisingly, our NANs show unconventional colloidal stability due to their unique nanoporous architectures.