Molecular Docking of Bioactive Compounds against Leukemia Protein Targets

Abstract

Cancer is one of the leading causes of death worldwide and is characterized by uncontrolled cell growth and the ability of abnormal cells to spread to other parts of the body. Among different types of cancer, leukemia is a serious blood cancer that affects the bone marrow and blood-forming tissues. Targeting specific proteins involved in cancer progression has become an important strategy in modern drug discovery. Molecular docking is a computational technique widely used to predict the interaction between small molecules and target proteins, helping researchers identify potential therapeutic compounds. The present study focuses on the molecular docking analysis of selected natural bioactive compounds against the FLT3 (FMS-like tyrosine kinase 3) receptor, which plays a significant role in the development and progression of acute myeloid leukemia. The compounds selected for this study include Curcumin, Resveratrol, Quercetin, Camptothecin, and Vincristine. Venetoclax was used as the standard drug for comparison. The three-dimensional structures of ligands were obtained from chemical databases and prepared using computational tools, while the receptor structure was retrieved from the Protein Data Bank. Docking simulations were carried out using Auto Dock software to evaluate binding affinity, ligand efficiency, inhibitory constant, and hydrogen bond interactions. The docking results indicated that Venetoclax exhibited the highest binding affinity with a binding energy of –8.83 kcal/mol. Among the tested compounds, Vincristine and Camptothecin showed comparatively stronger interactions with the FLT3 receptor, while Curcumin, Quercetin, and Resveratrol demonstrated moderate binding affinity. Hydrogen bond interactions with key amino acid residues further confirmed stable ligand–protein complexes. Overall, the study suggests that these natural compounds possess potential inhibitory activity against FLT3 and may serve as promising candidates for further experimental validation and drug development in leukemia treatment.

Introduction

Cancer is a disease caused by uncontrolled cell growth due to genetic mutations, often triggered by factors such as radiation, chemicals, infections, and lifestyle habits. Early detection is crucial for improving survival rates. This study focuses on identifying potential anticancer compounds by targeting the FLT3 protein, which is associated with acute myeloid leukemia.

A molecular docking approach was used to analyze the interaction between FLT3 and various natural and standard compounds, including curcumin, resveratrol, quercetin, vincristine, camptothecin, and the standard drug venetoclax. Computational tools such as AutoDock and PyMOL were used to evaluate binding affinity, hydrogen bonding, and inhibitory potential.

Results showed that venetoclax had the strongest binding affinity overall. Among the tested compounds, vincristine demonstrated the highest binding strength, followed by camptothecin, while curcumin, resveratrol, and quercetin showed moderate interactions. The presence of hydrogen bonds confirmed stable ligand–protein interactions.

Overall, the study suggests that these natural compounds, especially vincristine and camptothecin, have promising potential as anticancer agents targeting FLT3, supporting further research in drug development.

Conclusion

The docking study compared the interaction of natural compounds with the FLT3 protein against the standard drug Venetoclax. Venetoclax showed the strongest binding affinity (–8.83 kcal/mol). Among the tested natural compounds, Vincristine displayed relatively strong interaction followed by Camptothecin. Curcumin, Resveratrol and Quercetin showed moderate inhibitory potential. These compounds may serve as potential leads for further experimental and structural optimization in leukemia treatment.

References

[1] American Cancer Society. (2021). What is cancer? Retrieved from https://www.cancer.org/cancer/cancer-basics/what-is-cancer.html [2] American Cancer Society. (2021). Leukemia. Retrieved from https://www.cancer.org/cancer/leukemia.html [3] Rao, A. R., & Agarwal, R. (2010). Anticancer potential of natural products. In The Role of Phytochemicals in Cancer Chemoprevention (pp. 1-38). Springer. https://doi.org/10.1007/978-1-4419-1621-3_ [4] Khokhar, A. S., & Singh, A. (2014). Curcumin and its role in leukemia treatment. Cancer Chemotherapy and Pharmacology, 74(5), 1065-1074. https://doi.org/10.1007/s00280-014-2573-5 [5] Sharma, S., & Suman, S. (2014). Resveratrol and its role in cancer prevention and therapy: A review. Journal of Cancer Research and Clinical Oncology, 140(6), 1023-1032. https://doi.org/10.1007/s00432-014-1681-x [6] Rajni Bala, Reecha Madaan, Samrat Chauhan, Malika Gupta, Ankit Kumar Dubey, Ishrat Zahoor, Hemavathi Brijesh, Daniela Calina, Javad Sharifi-Rad. Revitalizing allicin for cancer therapy. Naunyn-Schmiedeberg’s Archives of Pharmacology 397 (2), 703-724, 2024. [7] Arshad Husain Rahmani, Mohammed A Alsahli, Ahmad Almatroudi, Mashael Abdullah Almogbel, Amjad Ali Khan, Shehwaz Anwar, Saleh A Almatroodi. The potential role of apigenin in cancer prevention and treatment. Molecules 27 (18), 6051, 2022. [8] Luis Miguel Guaman Ortiz, Paolo Lombardi, Micol Tillhon, Anna Ivana Scovassi. Berberine, an epiphany against cancer. Molecules 19 (8), 12349-12367, 2014. [9] Atif B Awad, Rajat Roy, Carol S Fink. ?-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. Oncology reports 10 (2), 497-500, 2003. [10] Kaio Murilo Monteiro Espíndola, Roseane Guimarães Ferreira, Luis Eduardo Mosquera Narvaez, Amanda Caroline Rocha Silva Rosario, Agnes Hanna Machado Da Silva, Ana Gabrielle Bispo Silva, Ana Paula Oliveira Vieira, Marta Chagas Monteiro. Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Frontiers in oncology 9, 541, 2019. [11] Vasiliki Zoi, Vasiliki Galani, Georgios D Lianos, Spyridon Voulgaris, Athanasios P Kyritsis, George A Alexiou. The role of curcumin in cancer treatment. Biomedicines 9 (9), 1086, 2021 [12] Mohamed Berrada, Alex Serreqi, F Dabbarh, A Owusu, Ajay Gupta, Shirley Lehnert.A novel non-toxic camptothecin formulation for cancer chemotherapy. Biomaterials 26 (14), 2115-2120, 2005 [13] Ruth Clark, Seong-Ho Lee. Anticancer properties of capsaicin against human cancer. Anticancer research 36 (3), 837-843, 2016. [14] Jayadev Raju, Rekha Mehta. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin. Nutrition and cancer 61 (1), 27-35, 2008. [15] Carolyn Bell, Susan Hawthorne. Ellagic acid, pomegranate and prostate cancer. Journal of Pharmacy and Pharmacology 60 (2), 139-144, 2008 [16] Hardeep Singh Tuli, Muobarak Jaber Tuorkey, Falak Thakral, Katrin Sak, Manoj Kumar, Anil Kumar Sharma, Utah Sharma, Aklank Jain, Vaishali Aggarwal, Anupam Bishayee. Molecular mechanisms of action of genistein in cancer: Recent advances. Frontiers in Pharmacology 10, 1336, 2019 [17] Yogeshwer Shukla. Cancer preventive properties of ginger: a brief review. Food and chemical toxicology 45 (5), 683-690, 2007 [18] Muhammad Imran, Bahare Salehi, Javad Sharifi-Rad, Tanweer Aslam Gondal, Farhan Saeed, Ali Imran, Muhammad Shahbaz, Patrick Valere Tsouh Fokou, Muhammad Umair Arshad, Haroon Khan, Susana G Guerreiro, Natália Martins, Leticia M Estevinho. Kaempferol: A key emphasis to its anticancer potential. Molecules 24 (12), 2277, 2019 [19] Yusuf Baran. Therapeutic potential of luteolin on cancer. Vaccines 11 (3), 554, 2023 [20] A Venket Rao, Sanjiv Agarwal. Role of antioxidant lycopene in cancer and heart disease. Journal of the American College of Nutrition 19 (5), 563-569, 2000. [21] Fuchsia Gold-Smith, Alyssa Fernandez, Karen Bishop. Mangiferin and cancer: Mechanisms of action. Nutrients 8 (7), 396, 2016. [22] Mariia Zadorozhna, Tiziana Tataranni, Domenica Mangieri. Piperine: role in prevention and progression of cancer. Molecular biology reports 46 (5), 5617-5629, 2019 [23] Lara Gibellini, Marcello Pinti, Milena Nasi, Jonas P Montagna, Sara De Biasi, Erika Roat, Linda Bertoncelli, Edwin L Cooper, Andrea Cossarizza. Quercetin and cancer chemoprevention. Evidence?based complementary and alternative medicine 2011 (1), 591356, 2011 [24] Jean Francois Savouret, Michel Quesne. Resveratrol and cancer: a review Biomedicine & pharmacotherapy 56 (2), 84-87, 2002. [25] Adam Kowalczyk, Carlo Ignazio Giovanni Tuberoso, Igor Jerkovi?. The role of Rosmarinic acid in cancer prevention and therapy: mechanisms of antioxidant and anticancer activity. Antioxidants 13 (11), 1313, 2024. [26] Reza Bayat Mokhtari, Narges Baluch, Tina S Homayouni, Evgeniya Morgatskaya, Sushil Kumar, Parandis Kazemi, Herman Yeger. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. Journal of cell communication and signaling 12 (1), 91-101, 2018 [27] Sanjeev Banerjee, Subhash Padhye, Asfar Azmi, Zhiwei Wang, Philip A Philip, Omer Kucuk, Fazlul H Sarkar, Ramzi M Mohammad. Review on molecular and therapeutic potential of thymoquinone in cancer. Nutrition and cancer 62 (7), 938-946, 2010 [28] Muthu K Shanmugam, Xiaoyun Dai, Alan Prem Kumar, Benny KH Tan, Gautam Sethi, Anupam Bishayee. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies Biochemical pharmacology 85 (11), 1579-1587, 2013. [29] You-Wen Zhang, Xiang-Ying Kong, Jin-Hua Wang, Guan-Hua Du. Vinblastine and vincristine. Natural Small Molecule Drugs from Plants, 551-557, 2018 [30] Prathapan Abeesh, Chandrasekaran Guruvayoorappan. The therapeutic effects of withaferin A against cancer: overview and updates Current Molecular Medicine 24 (4), 404-418, 2024

Copyright

Copyright © 2026 Kanimozhi B., Keerthana N., Kiruba Shiny S., Sr. Dr. S. Kulandai Therese . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.