In silico exploration of potential breast cancer drugs


  • Daneilys de Dios Hernández Universidad de Ciencias Médicas Pinar del Río.



Nitrosoline, Cathepsin B Inhibitors, Molecular Docking


Introduction: breast carcinoma is the most common neoplasm among women. One of the current problems is the emergence of drug resistance. Cathepsin B is a cysteine protease that is overexpressed in tumor tissue. The search for new therapeutic alternatives derived from the nitroxoline nucleus constitutes an encouraging solution against the disease.
Objective: to evaluate in silico potential cathepsin B inhibitors as therapeutic targets in the treatment of breast carcinoma.
Methods: from the PubChem database, 12 ligands derived from the nitrosoline nucleus were obtained, which were converted to 3D and their energy was minimized by applying the GAFF force field. The specific characteristics of the protease active site were determined with the Proteins Plus web server to carry out molecular docking studies with Autodock Tools.
Results: ligands 1511784, 14125599 and 45487202 showed a favorable affinity energy (ΔG=-5.56; -5.51 and -5.08 respectively) and inhibition constant by inhibiting key residues of the catalytic site of cathepsin B. The amino acids were: His199, His110, His111, Gln23 and Gly198. The main interaction was by hydrogen bonding.
Conclusions: nitrosoline contains anticancer properties. Ligands 1511784, 14125599 and 45487202 constitute potential drugs against breast cancer. Therefore, in silico analyzes reduce the cost of current research and contribute to the specificity and immunogenicity of therapies and pharmacological biosafety.


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Trayes KP, Cokenakes SE. Breast Cancer Treatment. American Family Physician. 2021 Aug; 104(2):171-8. Disponible en:

Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A, et al. Breast Cancer Statistics. CA Cancer J Clin. 2022 Dec; 72(6):524–18. Disponible en:

Waks A, Winer E. Breast cancer treatment a review. Rev Clinical Review and Education. 2019; 321(3): 3p. Disponible en:

Ministerio de Salud Pública. Anuario estadístico 2019 La Habana. MINSAP. Disponible en:

Watkins EJ. Overview of breast cancer. Journal of the American Academy of Pas. 2019 Oct; 32(10):13-5. Disponible en:

De Dios DH. Selección de blanco terapéutico en la catepsina B para el desarrollo de fármacos contra el cáncer de mama. Rev Ciencias Médicas. 2021; 25(5): 10p. Disponible en:

Aggarwal N, Sloane B. Cathepsin B: Multiple roles in cancer. Rev Proteomics Clin. Appl. 2014; 8(5): 427-11. Disponible en: 7.

Gondi C, Rao J. Cathepsin B as a cancer target. Rev Expert Opin Ther Targets. 2013; 17(3): 281–11. Disponible en:

Sosic I, Mitrovic´ A, Hrvoje C, Knez D, Brodnik HZ, Štefane B et al. Cathepsin B inhibitors: Further exploration of the nitroxoline core. Bioorganic & Medicinal Chemistry Letters. 2018; 28: 1239–9. Disponible en:

Xu N, Huang L, Li X, Watanabe M, Li C, Xu A et al. The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer. International Journal of Biological Sciences. 2019; 15(5): 919-9. Disponible en:

Xu N, Lin W, Sun J, Sadahira T, Xu A, Watanabe M et al. Nitroxoline inhibits bladder cancer progression by reversing EMT process and enhancing anti-tumor immunity. Journal of Cancer. 2020; 11(22): 6633-6641.

Mirkovic B, Markelc B, Butinar M, Mitrovic A, Sosic I, Gobec S, et al. Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity. Oncotarget. 2015; 6: 19027-42. Disponible en:

Mitrovic A, Kljun J, Sosic I, Ursic M, Meden A, Gobec S et al. Organoruthenated Nitroxoline Derivatives Impair Tumor Cell Invasion through Inhibition of Cathepsin B Activity. Inorganic Chemistry. 2019; 58(18): 12334-12347. Disponible en:

Ranjbar D, Reza M, Dehghani Z, Firuzi D, Edraki N, Khoshneviszadeh M. Dihydronaphthalenone chalconoid derivatives as potential cathepsin B inhibitors; design, synthesis, cytotoxicity evaluation and docking analysis. Braz. J. Pharm. Sci. 2021;57: 1-14. Disponible en:

Chitranshi N, Kumar A, Sheriff S, Gupta V, Godinez A, Saks D et al. Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation. Cells. 2021; 10(1946). Disponible en:

Naranjo F. Análisis in silico de la catepsina B de Fasciola hepática como diana terapéutica. REDVET [Internet]. 2009 [citado: 08/03/2021]; 10(2): 1-36. Disponible en:

Guadalupe W, Paucara B, Grados, R. Acomplamiento molecular: criterios prácticos para la selección de ligandos biológicamente activos e identificación de nuevos blancos terapéuticos. Rev.Cs.Farm. y Bioq. 2019; 7(2). Disponible en:



How to Cite

de Dios Hernández D. In silico exploration of potential breast cancer drugs. Interamerican Journal of Health Sciences [Internet]. 2024 Jan. 4 [cited 2024 Jun. 21];4:171. Available from:



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