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The key objective for establishing a new drug delivery system is to transport therapeutic medications in the body's circulatory system and deliver them to selected therapeutic spots. In the current study, 2-aminopyridine (2AP), a bioactive molecule, was wrapped around a metal oxide framework known as the Zeolite imidazole framework (ZIF-8) for efficient drug delivery in HepG2 cells. To begin with, an in-silico technique molecular docking to access the binding capability of 2AP with EGFR target, and it exhibited a score of −7.4 kcal/mol. The morphology of the nanoparticles was examined through SEM and TEM analysis, DLS and Zeta potential exhibited the particle size, stability and further elements and functional groups present in ZIF-8 and 2AP@ZIF-8 was examined through EDX, TGA, XRD, and FTIR analysis. The drug loading capacity of ZIF-8 was examined and the drug release efficiency of ZIF-8 for the delivery of 2AP was evaluated in the phosphate-buffered saline under different pH conditions and witnessed the pH-responsive and sustained drug release. The dose-dependent and time-dependent anticancer efficacy of 2AP@ZIF-8 nanoparticles treated HepG2 cells has been investigated through the in-vitro MTT assay method. The IC50 values of 2AP@ZIF-8 nanoparticles for 24, 48, and 72 h were observed to be 54.8, 48.5, and 45.3 μg/mL, respectively. The ZIF-8 and 2AP@ZIF-8 showed nontoxic to HEK293 cells. Overall, our findings showed that ZIF-8 offers a pH-responsive release of 2AP loaded and 2AP@ZIF-8 caused cell death in HepG2 cells, suggesting novel therapeutic approaches against hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Co‐delivering FDA‐approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5‐Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6‐311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (ΔE) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug‐likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5‐Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs. [ABSTRACT FROM AUTHOR]

The main aim of this study is to identify the structural stability of allo‐ocimenol and its molecular reactivity against breast cancer‐associated proteins to confirm its anti‐cancer capability using density function theory and molecular docking analysis. The structural optimization was carried out via the DFT/B3LYP technique with a 6‐311++G (d,p) basis set. The molecular geometry and vibrational assignments of the Allo‐Ocimenol molecule were analyzed through density functional theory (DFT). Through optimized molecular structure, the vibrational frequencies (FT‐IR and FT‐Raman) were assigned and related with experimentally observed vibrational frequencies and the UV spectrum was computed and experimentally confirmed. The allo‐ocimenol's reactive activity was further analyzed through a computed molecular electrostatic potential surface. Utilizing the HOMO‐LUMO energies and molecular electrostatic potential energy gap, the reactivity and molecular stability of the allo‐ocimenol molecule was calculated. Mulliken and natural population analyses were used to determine the charge distribution across the allo‐ocimenol atoms. The natural bond orbitals were used to demonstrate the bioactivity of the titled molecule. RDG evaluation was used to examine the weak interactions of the allo‐ocimenol molecule. ELF and LOL analyses were utilized to investigate the topology of the allo‐ocimenol molecule. Thermodynamic evaluation has been utilized to acquire values and asses the thermodynamic parameters that reveal the thermal stability of the title molecule. Allo‐Ocimenol's anti‐microbial activity was assessed through an in‐vitro disc diffusion method, and its tumor inhibitory and pharmacokinetic properties were evaluated through an in‐silico approach using molecular docking and ADMET investigation. Zones of clearance were seen in anti‐microbial analyses at various concentrations, and the breast cancer target protein NAMPT established the greatest binding potential, with a docking value of −7.4 Kcal mol−1. [ABSTRACT FROM AUTHOR]

Combination of FDA approved drugs may be more effective in biological activities by targeting different protein mechanism at a same time and less toxic. A combination of 5-Fluorouracil and tamoxifen may cause a synergistic effect and induce cancer cell death and more effective against corona virus. In this study, constructed 5-Fluorouracil with tamoxifen structure was optimized through DFT/B3LYP approach with the basis set 6-311 G. Theoretical, ultraviolet-visible spectrum was calculated, and electronic transitions were examined. The energy gap between HOMO and LUMO was used to study the combined structure's structural stability and reactivity and the computed energy gap (ΔE) was 4.3023825 eV. The Mulliken charge distribution was assessed and the atomic charges were calculated. The molecular docking simulation was performed with breast cancer and SARS-CoV-19 target proteins. The docking scores showed that the complex compound's binding affinity was higher, that confirms better synergistic effect of 5-Fluorouracil and tamoxifen. The complex compound's maximum binding affinity was −8.0 Kcal/mol against caspase 6 and −8.1 Kcal/mol against furin, that showed inhibitory potential against cancer and corona virus. The pharmacokinetic properties and toxicity of the complex structure was studied, and the results showed the safety profile of the complex lead compound and can be utilized as an effective anticancer and antiviral drug. [ABSTRACT FROM AUTHOR]