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. 2025 Jul 19;30(14):3032.
doi: 10.3390/molecules30143032.

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

Juliana Romano Lopes  1 , Freddy Humberto Marin-Dett  1 , Rita Alexandra Machado Silva  2 , Rafael Consolin Chelucci  3 , Lucília Saraiva  2 , Maria Emília Sousa  4   5 , Leonardo Luiz Gomes Ferreira  3 , Adriano Defini Andricopulo  3 , Paula Aboud Barbugli  6 , Jean Leandro Dos Santos  1
Affiliations

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

Juliana Romano Lopes et al. Molecules. .

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.

Keywords: anti-inflammatory; boronic acid; chalcones; head and neck cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Structural modification of chalcone-core.
Scheme 1
Scheme 1
General route for the obtained compounds (1–12).
Figure 2
Figure 2
Microscopy image of chalcone 5 following 24 h of incubation with NOK-si and SCC-25 cell models at a concentration of 9.45 μM each.
Figure 3
Figure 3
Annexin V-FITC/PI analysis of chalcone 5 carried out at three different concentrations: 44.3 μM, 22.1 μM, and 9.45 μM. Q1: Early necrotic cells; Q2: Late apoptotic cells; Q3: Viable cells; Q4: Early apoptotic cells.
Figure 4
Figure 4
Evaluation of chalcone 5 in reducing levels of (A) TNF, (B) IL-6, (C) IL-8, and (D) IL-1β in LPS-stimulated THP-1 cells at two different concentrations. Control (CT) = THP-1 cells not stimulated with LPS. * p < 0.05, ** p < 0.01, ns = not significant.
See this image and copyright information in PMC

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