In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Frontiers in Chemistry

Chemistry

Imran Zafar¹  Gezahign Fentahun Wondmie²  Abdel-Rhman Z. Gaafar³  Mohammed Bourhia⁴  Ahsanullah Unar⁵  Rohit Sharma⁶  Fakhar Un Nisa⁷  Rizwan -ur-Rehman⁸  Sania Riaz⁸  Arfa Safder⁹  Hassan Imran Afridi^1,10  Dileep Kumar^1,11 

[1] Department of Bioinformatics and Computational Biology, Virtual University Pakistan, Lahore, Pakistan;Department of Biology, Bahir Dar University, Bahir Dar, Ethiopia;Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia;Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco;Department of Precision Medicine, University of Campania “L. Vanvitelli”, Naples, Italy;Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, India;Depatment of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan;Faculty of Health and Life Sciences, Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad, Pakistan;Institute of Molecular Biology and Biotechnology, The University of Lahore, Punjab, Pakistan;National Center of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, Pakistan;UC Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA, United States;Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, India;Centre for Advanced Research in Pharmaceutical Sciences, Poona College of Pharmacy, Pune, India;

关键词: Nigella sativa;    breast cancer;    neuropilins;    oncogenes;    phytochemical screenings;    bioactive compounds;    molecular docking;    molecular dynamic simulation;   

DOI  :  10.3389/fchem.2023.1273149

 received in 2023-08-05, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments.Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability.Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C −80, C-120,C −150, C −200 ns) revealed strong hydrogen bonding in the complexes and showed −12.9, −11.6, and −11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis.Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

【 授权许可】

Unknown   
Copyright © 2023 Zafar, Safder, Imran Afridi, Riaz, -ur-Rehman, Unar, Un Nisa, Gaafar, Bourhia, Wondmie, Sharma and Kumar.

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