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Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods

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Abstract

Suppressing vascular endothelial growth factor (VEGF), its receptor (VEGFR2), and the VEGF/VEGFR2 signaling cascade system to inhibit angiogenesis has emerged as a possible cancer therapeutic target. The present work was designed to discover and evaluate bioactive phytochemicals from the Clerodendrum inerme (L.) Gaertn plant for their anti-angiogenic potential. Molecular docking of twenty-one phytochemicals against the VEGFR-2 (PDB ID: 3VHE) protein was performed, followed by ADMET profiling and molecular docking simulations. These investigations unveiled two hit compounds, cirsimaritin (− 12.29 kcal/mol) and salvigenin (− 12.14 kcal/mol), with the highest binding energy values when compared to the reference drug, Sorafenib (− 15.14 kcal/mol). Furthermore, only nine phytochemicals (cirsimaritin and salvigenin included) obeyed Lipinski’s rule of five and passed ADMET filters. Molecular dynamics simulations run over 100 ns revealed that the protein–ligand complexes remained stable with minimal backbone fluctuations. The binding free energy values of cirsimaritin (− 52.35 kcal/mol) and salvigenin (− 55.89 kcal/mol), deciphered by MM-GBSA analyses, further corroborated the docking interactions. The HOMO–LUMO band energy gap (ΔE) was calculated using density-functional theory (DFT) and substantiated using density of state (DOS) spectra. The chemical reactivity analyses revealed that salvigenin exhibited the highest chemical softness value (6.384 eV), the lowest hardness value (0.07831 eV), and the lowest ΔE value (0.1566 eV), which implies salvigenin was less stable and chemically more reactive than cirsimaritin and sorafenib. These findings provide further evidence that cirsimaritin and salvigenin have the ability to prevent angiogenesis and the development of cancer. Nevertheless, more in vitro and in vivo confirmation is necessary.

Graphical abstract

Illustration showing the work flow of screening of phytochemicals from C. inerme leaves for their anti-angiogenic potential.

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Data availability

All the data generated or analyzed during this study are included in this article. Any additional data needed are available upon request to the corresponding author.

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Acknowledgements

The authors would like to acknowledge Amity Institute of Biotechnology & Amity Institute of Pharmacy, Amity University Rajasthan, Jaipur for providing the needed facilities. The authors extend their appreciation to the Deanship of Scientific Research & Innovation, Ministry of Education in Saudi Arabia for the financial support through the project number IFP-IMSUI-2023107. The authors also appreciate the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU) for supporting this project.

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Authors and Affiliations

  1. Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India

    Nusrath Yasmeen, Sudarshan S. Lakhawat & Pushpender K. Sharma

  2. Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia

    Anis Ahmad Chaudhary

  3. Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia

    Salauddin Khan

  4. School of Life Science, Punyashlok Ahilyadevi Holkar Solapur University, Solapur, Maharashtra, India

    Priya Vijay Ayyar

  5. Amity Institute of Pharmacy, Amity University Rajasthan, Jaipur, Rajasthan, India

    Vikram Kumar

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  1. Nusrath Yasmeen
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Contributions

NY & VK conceptualized and designed this study, methodology, and was instrumental in investigation, analysis, drafting the entire manuscript with visualizations. AAC, SK, PVA, SSL, & PKS revised and edited the manuscript in its final form. All authors read and approved the final manuscript.

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Correspondence to Vikram Kumar.

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Yasmeen, N., Chaudhary, A.A., Khan, S. et al. Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10846-4

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