Molecular docking and biochemical insights into the pro-apoptotic cytotoxicity of <i>Breonadia salicina</i>

Iliyasu Uwaisu; Sawsan S. Al-Rawi; Ahmad H. Ibrahim; Abdulrahman Mahmoud Dogara; Ateeq Ahmed Al-Zahrani; Shehu Sani; Yakubu Yahaya; Sani Hammada; Garba Musa Abdullahi; Hussain D. Almalki; Alaa Ahmad Hamdy; Iliyasu Uwaisu; Sawsan S. Al-Rawi; Ahmad H. Ibrahim; Abdulrahman Mahmoud Dogara; Ateeq Ahmed Al-Zahrani; Shehu Sani; Yakubu Yahaya; Sani Hammada; Garba Musa Abdullahi; Hussain D. Almalki; Alaa Ahmad Hamdy

doi:10.3934/biophy.2025026

AIMS Biophysics

2025, Volume 12, Issue 4: 544-569. doi: 10.3934/biophy.2025026

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Research article

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

1.
Department of Pharmacognosy and Drug Development, Faculty of Pharmaceutical Sciences, Kaduna State University, Kaduna, Nigeria
2.
Biology Education Department, Tishk International University, Erbil, Iraq
3.
Pharmacy Department, Tishk International University, Erbil, Iraq
4.
Chemistry Department, University College at Al-Qunfudhah, Umm Al-Qura University, Saudi Arabia
5.
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences Kaduna State University, Kaduna, Nigeria
6.
Department of Community Medicine, Faculty Basic Medical Sciences, Kaduna State University, Kaduna, Nigeria
7.
Ministry of Health, Directorate of Health, Duhok, Kurdistan Region, Iraq

Received: 21 September 2025 Revised: 31 October 2025 Accepted: 12 November 2025 Published: 19 November 2025

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.
- medicinal plants,
- anticancer,
- apoptosis,
- antioxidants,
- cytotoxicity,
- phytochemicals,
- molecular docking
Citation: Iliyasu Uwaisu, Sawsan S. Al-Rawi, Ahmad H. Ibrahim, Abdulrahman Mahmoud Dogara, Ateeq Ahmed Al-Zahrani, Shehu Sani, Yakubu Yahaya, Sani Hammada, Garba Musa Abdullahi, Hussain D. Almalki, Alaa Ahmad Hamdy. Molecular docking and biochemical insights into the pro-apoptotic cytotoxicity of Breonadia salicina[J]. AIMS Biophysics, 2025, 12(4): 544-569. doi: 10.3934/biophy.2025026

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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.

Conflict of interest

All the authors declare and confirm that they have no conflicts of interest.

Author contributions

IU, SS, YY, SH, GMA: Carried out practical, AAA, HD; Molecular docking Analysis, SAR, AHI, AMD and AAH; Conceptualize the idea, analyze and drafted the manuscript. All authors read and approved the final version.

Availability of data and materials

The data that support the findings of this study are available in the article.

Ethical statement

The research was conducted in accordance with the protocol that was approved by the Health Research Ethical Clearance Committee of the College of Allied Health and Pharmaceutical Sciences, Kaduna State University, Kaduna, Nigeria (Ethical Approval No: Date 17/07/2020, A/CAP/KASU/20/259).

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