Exploring the Synergistic Effect of Tegafur-Syringic Acid Adduct Against Breast Cancer through DFT Computation, Spectroscopy, Pharmacokinetics and Molecular Docking Simulation

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Combining FDA‐approved medications may increase biological activity by simultaneously targeting many protein mechanisms while being less toxic. Gemcitabine and docetaxel together might have a synergistic impact that kills cancer cells and makes them more effective against breast cancer. This study used the foundation set B3LYP/6–311 G to optimize the gemcitabine with the docetaxel structure that was created. Theoretical calculations were made for the ultraviolet to visible spectrum were studied in gas and liquid phase. The structural stability and reactivity of the combined structure were studied using the energy gap between HOMO and LUMO, and the computed energy gap (ΔE) was 4.219 eV. The electrostatic potential of complex structure was determined and the Mulliken charge population was evaluated. Through RDG analysis weak interactions of GEDT was evaluated and topology properties were studied through ELF and LOL analysis. Breast cancer target proteins were utilized in the molecular docking studies. The docking scores revealed a greater binding affinity for the complex molecule, confirming a superior combinatorial interaction between gemcitabine and docetaxel. Highest binding ability of the GEDT was against Caspase‐6 and the network analysis of Caspase‐6 was assessed through graph theory model. The stability of GEDT with Caspase‐6 was studied through molecular dynamic simulation for 100 ns. The adsorption, distribution, metabolism, excretion, and toxicity characteristics of the complex structure were investigated, and the findings revealed the complex lead compound's safety profile and its potential for use as a potent anticancer medication.

Section: Resultsmentioning

confidence: 99%

“…and F C H were on the predicted range and were tabulated in Table S1b [42]. Karuppaasamy et al, reported theoretically and experimentally that C C bond in 5-fluorouracil and phenylalanine adduct has exhibited an average bond range 1.345 Å.…”

Section: Optimization and Structural Parameters Of Gedtmentioning

confidence: 97%

Exploring the co‐activity of FDA approved drug gemcitabine and docetaxel for enhanced anti‐breast cancer activity: DFT, docking, molecular dynamics simulation and pharmacophore studies

Sukumaran,

Zochedh,

Chandran

et al. 2024

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“…The oxygen atom possesses negative charge and all carbon atoms except C2 (0.305805e), C6 (0.141043e), C7 (0.09688e), and C8 (0.363855e) have negative charges, whereas these carbon atoms C2, C6, and C8 were connected to CH 3 replacement. This reveals that allo‐ocimenol has a more amount of charge delocalization [66].…”

Section: Resultsmentioning

confidence: 99%

Quantum chemical calculation, topological analysis, biological evaluation and molecular docking of allo‐ocimenol against breast cancer

Chandran,

Zochedh,

Sukumaran

et al. 2023

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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.

“…In addition, they also offer insights into the orbital occupancy and energy levels. Table S5 illustrates the evaluated outcomes of the decanal natural charges [44,45] and Figure 3F represents natural population charge grade of decanal. The analysis reveals that the atom C10 exhibits the highest electronegative charge with a value of À0.56918e, while C11 shows the most electropositive charge at 0.45252e.…”

Section: Natural Population Analysismentioning

confidence: 99%

Pharmacoinformatics and quantum chemicals‐based analysis of aromatic molecule decanal as a potent drug against breast cancer

Arumugam,

Chandran,

Zochedh

et al. 2024

This study's primary goal is to perform density functional theory and molecular docking simulation to determine decanal's structural stability and biological activity against proteins allied to breast cancer in order to validate its anti‐cancer potential. Initially, the drug‐likeness features of decanal was predicted and the outcomes confirmed that it is non‐toxic and follows Lipinski's rule. Through basis set 6‐311++G (d, p), the structural optimization was performed and molecular geometry was investigated. The FT‐IR and UV–Visible spectroscopic analysis was theoretically performed and validated via experimental analysis. The reactive surface of decanal was further investigated using a calculated molecular electrostatic potential surface. The molecular structural stability and bio‐reactivity of decanal was determined by using the HOMO‐LUMO energies and energy gap calculated is 6.215 eV. The charge distribution among the atoms of decanal was ascertained through the analysis of Mulliken and natural population distribution. To look at the decanal molecule's topological properties, electron localization function and localized orbital locator were used. The decanal's weak interactions were investigated via reduced density gradient assessment. The docking evaluation was performed against the proteins involved in breast cancer and the highest binding ability was calculated against the protein Bcl‐2 with the score of −6.5 kcal/mol. These theoretical findings will pave a way to understand the decanal's structural stability, reactivity and breast cancer inhibitory property and can be used as a drug candidate against tumor after in vitro and clinical evaluation.