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

TL;DR

This study designs and synthesizes boronic chalcones that show both anticancer and anti-inflammatory effects, particularly in head and neck cancer.

Contribution

The paper introduces a novel series of boronic chalcones with dual anticancer and anti-inflammatory activity.

Findings

Compound 5 showed cytotoxicity against SCC-25 cancer cells with an IC50 of 17.9 µM and a selectivity index >3.

Compound 5 reduced pro-inflammatory cytokines TNF and IL-6, indicating anti-inflammatory activity.

DMPK studies showed compound 5 has moderate solubility and high permeability.

Abstract

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 5 emerged as the most promising, displaying cytotoxicity against cancer cells, with IC50 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 5 also significantly reduced pro-inflammatory cytokine levels, as TNF and IL-6. Furthermore, drug metabolism and pharmacokinetics (DMPK) studies demonstrated that compound 5 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.

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