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Network pharmacology, molecular docking, and molecular dynamics simulation analysis reveal the molecular mechanism of halociline against gastric cancer

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Abstract

Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Notably, molecular docking and dynamics simulations revealed a high affinity between halociline and these targets, with free binding energies (ΔEtotal) of − 20.28, − 27.94, and − 25.97 kcal/mol for MAPK1, MMP-9, and PIK3CA, respectively. This study offers valuable insights into the potential molecular mechanism of halociline’s inhibition of gastric cancer cells and serves as a valuable reference for future basic research efforts.

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Funding

This study was supported by the Hainan Province Science and Technology Special Fund (Grant Nos. ZDYF2021SHFZ235, ZDYF2023SHFZ114) and the Hainan Provincial National Natural Science Foundation of China (Grant No. 522RC684).

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Author notes

  1. Xiangru Zha, Rong Ji, and Yang Li have contributed equally to this work and are treated as first authors.

Authors and Affiliations

  1. NHC Key Laboratory of Control of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, 3#, Xueyuan Road, Haikou, 571199, Hainan, China

    Xiangru Zha, Rong Ji, Yang Li, Rong Cao & Songlin Zhou

Authors
  1. Xiangru Zha
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  2. Rong Ji
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  3. Yang Li
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  4. Rong Cao
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  5. Songlin Zhou
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Contributions

RJ and SLZ contributed to conceptualization, supervision, investigation. XRZ and YL conducted molecular docking and dynamics studies. RJ and RC performed network pharmacology and analysis. RJ, XRZ, and YL performed methodology, software data analysis. XRZ and SLZ contributed to writing—original draft preparation.

Corresponding author

Correspondence to Songlin Zhou.

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Zha, X., Ji, R., Li, Y. et al. Network pharmacology, molecular docking, and molecular dynamics simulation analysis reveal the molecular mechanism of halociline against gastric cancer. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10822-y

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