Design and Synthesis of Boronic Chalcones with Dual Anticancer and Anti-Inflammatory Activity.

Head and neck cancer (HNC) is a highly aggressive malignancy with limited treatment options and poor prognosis. Inflammation plays a critical role in HNC progression, with elevated levels of pro-inflammatory cytokines such as TNF, IL-6, IL-8, and IL-1β contributing to tumor development. In this study, a novel series of boronic chalcones was designed and synthesized as potential dual-action anticancer and anti-inflammatory agents. The most potent compounds were evaluated for their cytotoxicity against Squamous Cell Carcinoma (SCC-25), and their selectivity index (SI) was determined. Compound emerged as the most promising, displaying cytotoxicity against cancer cells, with IC values of 17.9 µM and a favorable SI (>3). Mechanistic studies revealed that its anticancer activity was independent of p53 status, and annexin V/PI staining indicated cell death via necrosis. Interestingly, compound also significantly reduced pro-inflammatory cytokine levels, as TNF and IL-6. Furthermore, drug metabolism and pharmacokinetics (DMPK) studies demonstrated that compound exhibited moderate solubility and high permeability. These findings underscore the crucial role of the boronic acid moiety in enhancing both anticancer and anti-inflammatory properties.