Molecular modeling, synthesis, and antiproliferative evaluation of new isoxazole ring linked by Schiff bases and azo bond.

Lung cancer is the most common malignancy worldwide, with approximately 1.8 million new cases yearly. Cytotoxic drugs are frequently used in cancer treatment. Even though the medicine enhances patients' quality of life, several drawbacks diminish its efficacy. Drug resistance and many disadvantages associated with chemotherapeutic drug side effects continue to be significant factors limiting the efficiency of cancer treatment. This necessitates developing new effective strategies that target tumors with minimal adverse effects. This research aims to overcome these issues by synthesizing a new series of compounds with an isoxazole ring attached by Schiff bases and azo bonds based on molecular docking with the (Genetic Optimization of Ligand Docking) program and estimating the pharmacokinetic properties with the Swiss ADME. The greatest-fitting compounds were then manufactured and verified by spectral analysis (FT-IR, 1H NMR, and 13C NMR), in vitro MTT assay for assessment of antiproliferative activities against A549 lung cancer cell lines showed that compounds 5a and 5b had an inhibitory concentration half-maximal inhibitory concentration (IC50) (17.34 and 18.32 µM), respectively, which was significantly lower than the inhibitory concentration of erlotinib (IC50 = 25.06 µM).

Molecular Docking Study of New Sorafenib Analogues as Platelet-Derived Growth Factor Receptor Inhibitors for the Treatment of Cancer.

Cancer is a disease triggered by an uncontrolled growth of a group of cells usually from a single cell. Chemotherapy is a common and systematic therapy that involves the use of anticancer drugs also known as chemotherapeutical agents to treat cancer. Tyrosine kinases are a subset of protein kinases that are a family of over 90 enzymes that selectively phosphorylate tyrosine residues in various substrates. Receptors with internal tyrosine kinase activity mediate the actions of several growth factors, differentiation factors, and hormones, resulting in the reproduction and differentiation of the affected cells. In the fight against cancer, the platelet-derived growth factor receptor has emerged as a novel target via inhibition of this receptor resulting in the inhibition of tyrosine kinase cascade. Docking investigations were conducted using the Genetic Optimization for Ligand Docking (GOLD) Suite (v. 5.7.1) from the Cambridge Crystallographic Data Center. A high-definition X-ray crystallography of the platelet-derived growth factor protein [Protein Data Bank (PDB) ID 6JOL] was downloaded from the website PDB with a resolution of 2 A. Compounds II, III, VII, and VIII have greater binding energies than the GOLD standard medication sorafenib, which gives Piecewise Linear Potential (PLP) fitness value (85.3). Other ligands exhibit good inhibitory action and docking scores comparable to that of the reference ligand sorafenib.

Synthesis, molecular docking and anti-inflammatory evaluation of new trisubstituted pyrazoline derivatives bearing benzenesulfonamide moiety.

A new series of trisubstituted pyrazoline bearing benzenesulfonamide moiety 6a,b-10a,b were designed, synthesised and evaluated for their anti-inflammatory in vitro. Before starting the synthesis, docking study has been used to insert compounds within the COX-2 structure active site using celecoxib drug as a reference. Final compounds 6a,b-10a,b were synthesised by condensing chalcones bearing pyridine moiety 1a,b-5a,b with 4-hydrazinyl benzenesulfonamide hydrochloride. In vitro, their anti-inflammatory activity was assessed using egg-white paw edema method, they showed moderate to strong inhibitory activity. Notably, Compounds 6a (29.78%), 7a (28.43%), 9a (27.92%) and 10a (27.92%) exhibited significant percentage inhibition at 300 min and results are comparable with percentage inhibition drug celecoxib (22.67%) and this result is highly agreement with docking scoring study.