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image of Computational Screening of Natural Compounds Targeting VEGFR-2 for Anti-Angiogenic Therapy

Abstract

Background

Angiogenesis is the growth of new capillaries from existing blood vessels that supply oxygen and nutrients and provide gateways for immune surveillance. Abnormal vessel growth in terms of excessive angiogenesis is a hallmark of cancer. VEGFR-2 (vascular endothelial growth factor receptor 2) dominating the process of angiogenesis has led to the approval of therapeutic inhibitors and is becoming a promising target for anti-angiogenic drugs. Notwithstanding these successes, the clinical use of current VEGFR-2 blockers is more challenging than anticipated.

Objective

In this study, we employed computer-aided approaches to elucidate the potential inhibitors of VEGFR2 in order to tackle angiogenesis in tumour.

Methods

The phytochemicals were retrieved from the Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database and were virtually screened with the help of molecular docking. The study employed the prediction of the pIC value and cytotoxic property of the phytochemical against various cancer cell lines. The preclinical efficacy was predicted using the ADME/T profile of the compounds. PASS analysis was performed to predict the biological activity of the phytochemicals.

Results

The compounds, namely liquiritigenin, acacetin, and D-delta-tocotrienol stand out among all screened phytochemicals. Liquiritigenin showed -38.24 total binding free energy (PBTOT/GBTOT), while acacetin and D-delta-tocotrienol exhibited -43.01 and -53.91 PBTOT/GBTOT, respectively. Furthermore, these three compounds showed promising RMSD, Rg, and SASA trajectories, which signifies their stability with the VEGFR2. Their ADME/T profile exhibited their preclinical safety.

Discussion

Liquiritigenin, acacetin, and D-delta-tocotrienol demonstrated strong binding to VEGFR-2, with binding free energies of -38.24, -43.01, and -53.91 PBTOT/GBTOT, respectively, suggesting potential as anti-angiogenic agents. Stable RMSD, Rg, and SASA trajectories and favorable ADME/T profiles support their preclinical safety. However, experimental validation is needed to confirm efficacy and specificity, as the study relies solely on computational methods. Future and studies are essential for clinical translation.

Conclusion

The results from various computational analyses suggest that these three phytochemicals, namely, liquiritigenin, acacetin, and D-delta-tocotrienol, could possibly serve as potent VEGFR2 inhibitors to control the development of angiogenesis and tumorigenesis. However, experimental validation is required to test their efficacy as the study is solely based on a computational approach.

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2025-07-07
2025-12-15

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Computational Screening of Natural Compounds Targeting VEGFR-2 for Anti-Angiogenic Therapy
Bentham Science Publishers ; https://doi.org/10.2174/0122102981375849250623091708
/content/journals/cset/10.2174/0122102981375849250623091708
/content/journals/cset/10.2174/0122102981375849250623091708
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  • Article Type:     Research Article
Keywords: tumour ; cancer ; in silico ; VEGFR ; MD simulation ; Angiogenesis
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