Sultan Asath Bahadur

A cocrystal of the anticancer drug 5-fluorouracil with thiourea (5FUTU) was synthesized and single crystal was grown by slow solvent evaporation. Single-crystal X-ray diffraction (SCXRD) established the unit cell parameters and powder X-ray diffraction (PXRD) confirmed the formation and phase purity of the cocrystalline phase. Hirshfeld surface analysis and the associated two-dimensional fingerprint plots were used to identify the intermolecular interactions governing crystal packing and to quantify their relative contributions. The functional groups in 5FUTU were characterized by Fourier-transform infrared (FTIR) spectroscopy and its electronic absorption behaviour was examined by UV-Vis spectroscopy. Density functional theory (DFT) calculations were performed to support the experimentally determined crystal structure and to elucidate the spectroscopic and electronic properties of the cocrystal. The calculations included frontier molecular orbital (HOMO-LUMO) energies, natural and Mulliken population analyses, Fukui functions to gain further insight into its electronic distribution, chemical reactivity and stability. The biological potential of 5FUTU was evaluated by molecular docking and an in vitro MTT cytotoxicity assay. Molecular docking revealed favourable binding of 5FUTU to glycogen synthase kinase-3β (GSK-3β), with a binding energy of -6.6 kcal/mol. The MTT assay showed cytotoxic activity against MDA-MB-231 breast cancer cells, with an IC50 of 46.7 µM. Pharmacokinetic analysis assessed its drug-likeness and support further investigation of 5FUTU in structure-based drug design for breast cancer therapy.

This study explores the combinatorial potential of carvacrol‐lawsone adduct (CALA) by analyzing its structural, electronic, and binding features against breast cancer–associated targets. Density functional theory (DFT) calculations optimized the CALA structure, revealing band gap energies of 2.036 eV (without GD3) and 1.917 eV (with GD3), suggesting favorable electronic reactivity. Molecular electrostatic potential mapping highlighted regions of charge depolarization, while Mulliken and Natural Population Analyses provided insights into atomic charge distribution. The electronic topology was further characterized using the electron localization function (ELF) and localized orbital locator (LOL), whereas reduced density gradient (RDG) and non‐covalent interaction (NCI) analyses clarified intermolecular interactions. Pharmacokinetic predictions indicated drug‐like properties, and molecular docking revealed strong affinity of CALA toward AKT1 with a binding energy of −11.4 kcal/mol. Molecular dynamics simulations supported the stability of the CALA+AKT1 complex, showing consistent root mean square deviation (RMSD) values (2.5–3.0 Å) and root mean square fluctuation (RMSF) below 3.0 Å. Collectively, CALA demonstrates favorable reactivity, structural stability, pharmacological potential, and strong AKT1 interaction. These findings propose CALA as a promising combinatorial candidate for targeting AKT1 to inhibit breast cancer progression, although further in vitro and in vivo validation is necessary to establish its therapeutic applicability.

Breast cancer is the most diagnosed cancer in women globally, with millions of new cases each year. AKT‐1 plays a significant role in the development and progression of breast cancer, as it is a critical part of the PI3K/AKT/mTOR signaling pathway, which regulates several cellular processes. The current work was focused on assessing the structural stability and reactive potential of allyl sulfide using density functional theory method, and geometric parameters were calculated. IR and Raman frequencies were simulated, and the vibrational wavenumbers were examined. The electronic spectroscopy was determined in the gaseous phase through TD‐DFT technique, and the transition allotted for allyl sulfide was σ → σ*. The calculated energy between HOMO and LUMO was 5.597 eV, confirming better stability of allyl sulfide. Allyl sulfide's electrophilic and nucleophilic characteristics, reactive zone, charge distribution across atoms, and topological properties were studied. The drug‐likeness attributes of allyl sulfide were confirmed through pharmacophore studies, confirming its safety profile. Docking experiments showed that allyl sulfide had a higher binding score with the AKT‐1 protein (−6.8 kcal/mol). Molecular dynamics simulation was used to evaluate the stability of the AKT‐1 and allyl sulfide complex throughout a 100 ns run. The MTT assay revealed the cytotoxic effect of allyl sulfide in T47‐D cells. The effectiveness of allyl sulfide as a breast cancer treatment was assessed using in silico and in vitro techniques, including docking, MD simulation, MTT assay, and the ADMET study to reveal drug safety features.

In this study, the structure of 1,3,5‐trihydroxybenzene (135THB) was investigated using powder X‐ray diffraction and compared with simulated geometry. Its optimized molecular structure was analyzed for vibrational modes, electronic transitions, and interactions with breast cancer target proteins. Theoretical IR and UV–visible spectra were calculated and correlated with experimental data. Quantum chemical parameters, including reactive sites, atomic charges, and frontier molecular orbitals, were examined using density functional theory (DFT). Topological analysis and Hirshfeld surface mapping provided insights into molecular bonding and intermolecular interactions. Molecular docking with six breast cancer‐related proteins demonstrated favorable binding affinities, with the strongest interaction observed with AKT1 (−7.1 kcal/mol). This complex was further validated through a 100‐ns molecular dynamics simulation. ADMET and pharmacokinetic evaluations indicated that 135THB possesses good drug‐likeness and bioavailability. Overall, this work combines experimental spectroscopy, DFT calculations, multitarget docking, and molecular dynamics simulation, proposing 135THB as a promising candidate for future in vitro and in vivo anticancer studies.

Esophagogastric junction carcinoma is a prominent cause of cancer fatalities and is lethal for patients with metastases and a future occurrence. About 10–20% of gastric and esophagogastric junction cancers overexpress HER-2. For individuals who might benefit from targeted therapy with anti-HER-2 medications, HER-2 targeting is essential in various cancer types. The main objective of this work is to assess the anti-cancer potential of 4-(2-amino-2-carboxyethyl) imidazole (4-2A2CI) by using density functional theory and molecular docking modeling to ascertain its structural stability and biological activity against proteins linked to esophagogastric cancer. The molecular arrangement was examined and structural optimization was carried out using the basis set CC-pVDZ. The reactive surface of 4-2A2CI was further examined using a computed molecular electrostatic potential field and the UV–Visible spectroscopy investigation was theoretically accomplished. The HOMO-LUMO energies and the predicted energy gap of 5.36 eV were used to assess the molecule structural stability and bioreactivity of 4-2A2CI. The binding ability was determined to be −6.7 kcal/mol after the docking study was conducted against the protein HER-2 implicated in esophagogastric cancer. Using in vitro methods, the cell viability, morphological examination and apoptosis of AGS cells treated with 4-2A2CI were investigated. 4-2A2CI showed an IC[ ] dosage of 60.9 [ ]M in AGS cells following the 24-hour treatment. Further, expression level of HER-2 in AGS after treatment was validated and showed reduced HER-2 expression levels. Overall outcomes showed 4-2A2CI reduced HER-2 expression and led to apoptosis-related cell death in AGS cells for treatment of esophagogastric junction cancer.

The 6‐mercaptopurine syringic acid (6MPSY) a new drug–drug cocrystal has been synthesized by the neat grinding method. The prepared cocrystal 6MPSY has been screened by the powder x‐ray diffraction procedure and the single phase was confirmed. Using density functional theory with B3LYP/6‐311++G (d, p) source set, the structural parameters were computed and associated with the structural parameters of the 6‐mercaptopurine molecule and syringic acid molecule reported earlier exhibit good agreement. Experimental FTIR and UV–vis spectra were documented to identify and analyze the group vibrational frequencies and electronic behavior of the cocrystal. The NBO study was accomplished and the inter‐ and intra‐molecular interactions were established. The inspection of the topological (MEP, ELF, LOL) and non‐covalent (RDG, IRI, DORI) contacts has exposed diverse groups of inter‐ and intra‐molecular links on the source of electron localization density and color gauge pointer, respectively. Mulliken and natural atomic charges have been calculated and depicted. Fukui studies gave the reactive site with high f⁺ and f⁻ for C10, C17, C33, and H14 of the drug–drug cocrystal. The FMO analysis exhibits a low energy gap of 3.7612 eV that shows the efficiency of the drug–drug cocrystal in terms of chemical reactivity and stability. In addition, the thermodynamical parameters were calculated. The anti‐breast cancer activity of 6MPSY was investigated through in silico and in vitro analysis. The docking outcomes of 6MPSY range between −7.5 and −9.3 kcal/mol, and the calculated IC₅₀ value in MDA‐MB‐231 breast cancer cells was 83.2 μg/mL.