Repurposing Nafithromycin for Lung Cancer Therapy: Targeting Urokinase-Type Plasminogen Activator (uPA) via Molecular Docking and Dynamics Study
نویسندگان
1 Department of Pharmacology, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
2 Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
3 Department of Pharmaceutical Chemistry, N.B.S Institute of Pharmacy, Ausa, latur, Maharashtra, India
4 Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
5 Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Bab-Al-Mouadam-10001, Baghdad, Iraq
6 Department of Pharmacology, CSRI Lab, Vishnu Institute of Pharmaceutical Education & Research, Vishnupur, Narsapur, Medak District, Telangana, 502 313, India
7 Department of Pharmaceutical Chemistry, Audisankara College of Pharmacy , Gudur, Andhra Pradesh, India
8 Department of Pharmaceutical Sciences, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
doi
10.48309/chemm.2025.508638.1909چکیده
Lung cancer remains the leading cause of cancer-related deaths worldwide, demanding urgent advancements in early detection and targeted therapy. This study aimed to explore the potential of Nafithromycin for treating lung cancer by targeting the urokinase-type plasminogen activator (uPA), which is linked to tumor growth and metastasis. Molecular docking revealed that Nafithromycin had a higher binding affinity (-8.2 kcal/mol) than the native ligand (-6.9 kcal/mol). MD simulations over 100 ns revealed the stable formation of the drug, which included strong hydrogen bonds with key residues, such as HIS55, GLY228, and SER226. Nafithromycin, like azithromycin and clarithromycin, can be combined with anticancer agents to increase their efficacy in lung cancer treatment. Nafithromycin has the potential repurposed as an anticancer agent by targeting the uPA system, supporting further research on lung cancer treatment.
