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Background <p>The elevated mortality associated with ovarian cancer arises from delayed detection, recurrent disease, and the rapid emergence of chemoresistance. This study assesses the anticancer efficacy of two synthetic curcumin analogues, B-143 and B-155, in comparison to natural curcumin, employing SKOV3 ovarian cancer cells as the experimental model.</p> Objective <p>The aim of this study was to determine whether structural alterations to the analogues enhanced their functional performance.</p> Methods and Results <p>Through assays assessing cytotoxicity, cell-cycle distribution, apoptosis, and migration, the findings revealed that B-155 exhibited significantly greater cytotoxicity compared to curcumin and B-143, which was associated with G2/M cell-cycle arrest and increased apoptosis. Furthermore, both B-155 and curcumin effectively suppressed SKOV3 cell migration, whereas B-143 displayed minimal effects. Network pharmacology analyses predicted that B-143 and B-155 interact with overlapping yet distinct angiogenesis- and metastasis-associated signaling networks, suggesting potential associations with multiple signaling pathways relevant to ovarian cancer. Moreover, RT-qPCR reveals curcumin consistently downregulated the expression of genes linked to epithelial-mesenchymal transition (EMT) and cellular stress, whereas B-143 and B-155 displayed only partial adaptive responses in several angiogenesis and metastasis transcription markers. To further explore the molecular basis of B-155 activity, molecular docking and molecular dynamics simulations were performed using MAPK14 (p38α MAPK) as a candidate target. Computational analyses demonstrated favorable binding of B-155 within the MAPK14 ATP-binding pocket and stable protein–ligand complex formation throughout a 100 ns simulation.</p> Conclusion <p>B-155 demonstrated more significant anticancer activity than B-143, suggesting superior structural change-enhanced effectiveness. This research highlights the influence of structural modifications on curcumin’s biological activity, supports B-155 as a promising curcumin analogue for further investigation with anti-proliferative and migration suppressive properties, and emphasizes the need to incorporate both phenotypic and network-level assessments together with structural interaction analyses in curcumin-based drug development for ovarian cancer.</p>

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Pharmacological evaluation reveals distinct anti-proliferative and migration-associated effects of curcumin analogues B-143 and B-155 in ovarian cancer cells

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Retno Murwanti,
  • Rosalina Diani Prima Anargya,
  • Bakti Wahyu Saputra,
  • Zuhra Nur Jauza Ozura,
  • Nadzifa Nugraheni,
  • Sisca Ucche,
  • Navista Sri Octa Ujiantari,
  • Ritmaleni Ritmaleni,
  • Agung Endro Nugroho

摘要

Background

The elevated mortality associated with ovarian cancer arises from delayed detection, recurrent disease, and the rapid emergence of chemoresistance. This study assesses the anticancer efficacy of two synthetic curcumin analogues, B-143 and B-155, in comparison to natural curcumin, employing SKOV3 ovarian cancer cells as the experimental model.

Objective

The aim of this study was to determine whether structural alterations to the analogues enhanced their functional performance.

Methods and Results

Through assays assessing cytotoxicity, cell-cycle distribution, apoptosis, and migration, the findings revealed that B-155 exhibited significantly greater cytotoxicity compared to curcumin and B-143, which was associated with G2/M cell-cycle arrest and increased apoptosis. Furthermore, both B-155 and curcumin effectively suppressed SKOV3 cell migration, whereas B-143 displayed minimal effects. Network pharmacology analyses predicted that B-143 and B-155 interact with overlapping yet distinct angiogenesis- and metastasis-associated signaling networks, suggesting potential associations with multiple signaling pathways relevant to ovarian cancer. Moreover, RT-qPCR reveals curcumin consistently downregulated the expression of genes linked to epithelial-mesenchymal transition (EMT) and cellular stress, whereas B-143 and B-155 displayed only partial adaptive responses in several angiogenesis and metastasis transcription markers. To further explore the molecular basis of B-155 activity, molecular docking and molecular dynamics simulations were performed using MAPK14 (p38α MAPK) as a candidate target. Computational analyses demonstrated favorable binding of B-155 within the MAPK14 ATP-binding pocket and stable protein–ligand complex formation throughout a 100 ns simulation.

Conclusion

B-155 demonstrated more significant anticancer activity than B-143, suggesting superior structural change-enhanced effectiveness. This research highlights the influence of structural modifications on curcumin’s biological activity, supports B-155 as a promising curcumin analogue for further investigation with anti-proliferative and migration suppressive properties, and emphasizes the need to incorporate both phenotypic and network-level assessments together with structural interaction analyses in curcumin-based drug development for ovarian cancer.