Molecular docking and biochemical insights into the pro-apoptotic cytotoxicity of Breonadia salicina

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Abstract

The investigation of phytochemicals in plants has garnered substantial interest because of their potential therapeutic applications and pharmaceutical industries. These compounds can interact with biological systems, influencing critical biochemical mechanisms such as apoptosis, cell signaling, and oxidative stress. Therefore, understanding the mechanisms of action of these compounds is crucial to unlock their potential for developing novel agents for pharmaceuticals and health-promoting supplements. Breonadia salicina is a native species distributed throughout tropical and subtropical countries. This plant is used to treat of wounds, ulcers, fevers, headaches, gastrointestinal illness, cancer, arthritis, diabetes, inflammation, and bacterial and fungal infections. The roots were extracted via successive solvent extractions and evaluated for their antioxidant, phytochemical, and anticancer properties, with an emphasis on their apoptotic and underlying potential mechanisms. The ethanolic (REE), aqueous (AQR), ethyl acetate (EAR), and n-butanol (NBR) fractions significantly inhibited HT-29 cancer cells (p < 0.05). The EAR fractions displayed the strongest inhibition (IC₅₀ of 22.5 µg/mL) and promptly triggered early and late apoptosis and cell necrosis (p < 0.001). The EAR fractions demonstrated powerful TFC (19.4 Quercetin/g) activity, with IC₅₀ values of 22 and 25 mg/ml for ABTS and DPPH, respectively. LC‒MS/LC‒HRM analysis revealed several phytochemicals in the EAR fractions that contributed to the potential properties of the plants, including polyphenols, coumarin derivatives, 4,5-dicaffeoylquinic acid, chlorogenic acid, glycosides, and geniposidic acid. Notably, the in-silico cytotoxicity of these phytochemicals revealed the significant cytotoxicity of four potent compounds against six colon cancer cell lines, which presented the greatest interaction with the CDK2 enzyme (− 5.0 kcal/mol). These findings underscore the potential of the identified phytochemicals as promising anticancer or nutraceutical candidates for drug development and in the pharmaceutical industry.

Keywords

medicinal plants / anticancer / apoptosis / antioxidants / cytotoxicity / phytochemicals / molecular docking

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