cnf-2024 and Colorectal-Neoplasms

A major cause of failure of therapy in patients with non-small cell lung cancer (NSCLC) is development of acquired drug resistance leading to tumor recurrence and disease progression. In addition to the development of new generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), different molecular targets may provide opportunities to improve the therapeutic outcomes. In this study, we utilized the core structure 5-fluorouracil (5-FU) or tegafur, a 5-FU prodrug combined through different linkers with resorcinol to generate a series of fluoropyrimidin-2,4-dihydroxy-5-isopropylbenzamides which inhibit potent Heat Shock Protein 90 (HSP90). These compounds were found to show significant antiproliferative activity in colorectal cancer (CRC) HCT116 and NSCLC A549, H460, and H1975 (EGFR L858R/T790 M double mutation) cells. Compound 12c, developed by molecular docking analysis and enzymatic assays exhibits promising inhibitory activity of HSP90. This compound, 12c shows the most potent HSP90 inhibitory activity with an IC

Topics: Antineoplastic Agents; Apoptosis; Benzamides; Carcinoma, Non-Small-Cell Lung; Caspases; Cell Line, Tumor; Colorectal Neoplasms; Cytoprotection; Enzyme Activation; ErbB Receptors; Humans; Inhibitory Concentration 50; Lung Neoplasms; Mutation; Proteolysis; Proto-Oncogene Proteins c-akt