2. Academic Validation
  3. Novel 4-quinolone derivative inflicted cytotoxicity via intrinsic apoptotic pathway activation on human metastatic triple-negative breast cancer cells

Novel 4-quinolone derivative inflicted cytotoxicity via intrinsic apoptotic pathway activation on human metastatic triple-negative breast cancer cells

  • Bioorg Chem. 2025 Oct:165:109033. doi: 10.1016/j.bioorg.2025.109033.
Nursyuhada Azzman 1,  Muhammad Shoaib Ali Gill 2,  Nurshariza Abdullah 3,  Denisse A Gutierrez 4,  Armando Varela-Ramirez 4,  Laura A Sanchez-Michael 4,  Jose A Lopez-Saenz 4,  Mohamad Nurul Azmi Mohamad Taib 5,  Syed Adnan Ali Shah 6,  Renato J Aguilera 4,  Nafees Ahemad 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA, Cawangan Pulau Pinang Kampus Bertam, Kepala Batas 13200, Pulau Pinang, Malaysia.
  • 2 Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan.
  • 3 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia.
  • 4 Cellular Characterization and Biorepository Core Facility, Border Biomedical Research Center, Department of Biological Sciences, College of Science, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968-0519, United States of America.
  • 5 Natural Products and Synthesis Organic Laboratory (NPSO Lab), School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.
  • 6 Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam 42300, Selangor, Malaysia; Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam 42300, Selangor, Malaysia.
  • 7 School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia. Electronic address: nafees.ahemad@monash.edu.
PMID: 41043329 DOI: 10.1016/j.bioorg.2025.109033
Abstract

Quinolones are a class of compounds that have shown promising potential as Anticancer agents. However, the current quinolones in clinical trials are currently hampered by their efficacy issues. Therefore, we designed and synthesized novel 4-quinolone-3-carboxamide derivatives 14-67. All the synthesized compounds were initially screened for their cytotoxicity activity using the MTT assay method and evaluated for their Anticancer activities against leukemia and breast Cancer cells using the Differential Nuclear Staining (DNS) assay. Six screened compounds exhibited low CC50 inhibitory effects against breast Cancer cell lines, where compounds 24, 25, 52, and 65 also showed good activity (CC50 = 6.99-11.17 μM) against the leukemia cell line (Jurkat). In vitro assessment showed that the most active compound, 65, exhibited significantly higher growth inhibition activity (CC50 = 7.10-83.2 μM) in breast Cancer cell lines, with less cytotoxicity observed in non-cancerous cells (MCF-10 A). The most active analog, compound 65, triggered Apoptosis via membrane depolarization and caused cell cycle arrest at the S phase in the MDA-MB231/LM2-4 cell line. In conclusion, the outcomes indicate that compound 65 exhibits the potential to be a potent and effective Anticancer agent, making it an excellent candidate for further research and development.

Keywords

Anticancer agents; Antitumor agents; Apoptosis; Cytotoxic activity; Quinolones.

Figures
Products