The use of an appropriate delivery system capable of protecting, translocating, and selectively releasing therapeutic moieties to desired sites can promote the efficacy of an active compound. In this work, we have developed a nanoformulation which preserves its magnetization to load a model anticancerous drug and to explore the controlled release of the drug in a cancerous environment. For the preparation of the nanoformulation, self-assembled magnetic nanospheres (MNS) made of superparamagnetic iron oxide nanoparticles were grafted with a monolayer of (3-aminopropyl)triethoxysilane (APTES). A direct functionalization strategy was used to avoid the loss of the MNS magnetization. The successful preparation of the nanoformulation was validated by structural, microstructural, and magnetic investigations. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to establish the presence of APTES on the MNS surface. The amine content quantified by a ninhydrin assay revealed the monolayer coverage of APTES over MNS. The monolayer coverage of APTES reduced only negligibly the saturation magnetization from 77 emu/g (for MNS) to 74 emu/g (for MNS-APTES). Detailed investigations of the thermoremanent magnetization were carried out to assess the superparamagnetism in the MNS. To make the nanoformulation pH-responsive, the anticancerous drug Nintedanib (NTD) was conjugated with MNS-APTES through the acid liable imine bond. At pH 5.5, which mimics a cancerous environment, a controlled release of 85% in 48 h was observed. On the other hand, prolonged release of NTD was found at physiological conditions (i.e., pH 7.4). In vitro cytotoxicity study showed dose-dependent activity of MNS-APTES-NTD for human lung cancer cells L-132. About 75% reduction in cellular viability for a 100 μg/mL concentration of nanoformulation was observed. The nanoformulation designed using MNS and monolayer coverage of APTES has potential in cancer therapy as well as in other nanobiological applications.

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Over the centuries, cancer has been considered one of the significant health threats. It holds the position in the list of deadliest diseases over the globe. In women, breast cancer is the most common among many cancers and is the second most common cancer all over the world, while lung cancer is the first. Cyclin-dependent kinase 8 (CDK8) has been identified as a critical oncogenic driver that is found in breast cancer and associated with tumor progression. Flavonoids were virtually screened against CDK8 using molecular docking, drug-likeness, ADMET prediction, and a molecular dynamics (MD) simulation approach to determine the potential flavonoid structure against CDK8. The results indicated that ZINC000005854718 showed the highest negative binding affinity of −10.7 kcal/mol with the targeted protein and passed all the drug-likeness parameters. Performed molecular dynamics simulation showed that docked complex systems have good conformational stability over 100 ns in different temperatures (298, 300, 305, 310, and 320 K). The comparison between calculated binding free energy via MM/PB(GB)SA methods and binding affinity calculated via molecular docking suggested tight binding of ZINC000005854718 with targeted protein. The results concluded that ZINC000005854718 has drug-like properties with tight and stable binding with the targeted protein.

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Limonoids serve as vital secondary metabolites. Citrus limonoids show a wide range of pharmacological potential. As a result of which limonoids from citrus are of considerable research interest. Identification of new therapeutic molecules from natural origins has been widely adopted as a successful strategy in drug discovery. The current work mainly focused on the high-throughput computational exploration of the antiviral potential of three vital limonoids i.e. Obacunone, Limonin, and Nomilin against spike proteins of SARS CoV-2 (PDB:6LZG), Zika virus NS3 helicase (PDB:5JMT), Serotype 2 RNA dependent RNA polymerase of dengue virus (PDB:5K5M). Herein we report the molecular docking, MD simulation studies of nine docked complexes, and density functional theory of selected limonoids. The results of this study indicated that all three limonoids have good molecular features but out of these three obacunone exerted satisfactory results for DFT, docking, and MD simulation study.

Background Capparis zeylanica Linn. leaf extract was subjected to phytochemical screening for the determination of antioxidant and anticancer activity on (MCF-7) human breast cancer cells. The phytoconstituents previously determined were subjected to molecular docking studies against human epidermal growth factor receptor 2 (HER2) protein as a target receptor to support antioxidant and anticancer activities. Results Powdered plant leaves were extracted by maceration method using ethyl acetate, chloroform, methanol, ethanol and distilled water. Preliminary phytochemical evaluation and total phenolic and flavonoid content of the extract were evaluated using biochemical tests. Total antioxidant capacity of the extract was evaluated using different assays. Anticancer potential of methanolic and ethanolic extracts was studied on human breast cancer cells. Molecular docking studies were performed to evaluate the binding interactions of phytoconstituents on HER2 protein using AutoDock Vina. Phytochemical evaluation confirmed the presence of saponins, flavonoids, tannins, phenols, carbohydrates and proteins. Ethanolic extract showed a maximum total phenolic and flavonoid content in support with antioxidant and anticancer activities. The ethanolic leaf extract showed 66.63% cell growth inhibition against MCF-7 cells. Molecular docking studies revealed the highest binding affinity (− 8.4 Kcal/mol) of α-amyrin followed by quercetin and β-carotene. Glucocapparin, syringic acid, vanillic acid and p-coumaric acid showed almost a similar binding affinity to the amino acid residues of HER2 protein as compared to 5-FU. Conclusion C. zeylanica leaf extract showed the presence of phenolic and flavonoid constituents responsible for antioxidant and in vitro anticancer activities. Molecular docking studies showed the binding affinity of phytoconstituents on targeted HER2 protein.

A QSPR approach to the development of targeted formulation could save time and cost by early prediction of the most influential ingredient properties.