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<p>Selective dual inhibition of cyclooxygenase (COX-2) and HER-2 offers a novel approach for treating inflammation-driven malignancies. In this study, a series of camphor-derived thiocarbamates (<b>S1–S10</b>) was synthesized by condensing camphor thiosemicarbazone, functionalizing with chloroacetyl chloride, and subsequent nucleophilic derivatization to create diverse heterocyclic and aromatic structures. IR and NMR spectroscopy confirmed the designed frameworks. Molecular docking studies demonstrated higher affinity of compounds <b>S1</b> and <b>S2</b> for COX-2 (ΔG = − 106.82 and − 109.44&#xa0;kcal/mol) and HER-2 (ΔG = − 99.45 and − 99.80&#xa0;kcal/mol), with multiple stabilizing hydrogen bonds. Enzymatic assays showed potent COX-2 inhibition (IC<sub>50</sub> = 0.814 and 0.757 µM) and high selectivity over COX-1, matching the reference drug celecoxib. Both <b>S1</b> and <b>S2</b> demonstrated strong cytotoxicity against MCF-7 breast cancer cells (IC<sub>50</sub> = 2.70 and 2.60 µM), comparable to doxorubicin and superior to dasatinib. ADMET profiling indicated favorable absorption, metabolism, and safety properties. Overall, these results identify <b>S1</b> and <b>S2</b> as potent, drug-like dual COX-2/HER-2 inhibitors with broad anti-inflammatory/anticancer efficacy, supporting further preclinical evaluation as candidates for targeted therapy in inflammation-associated cancers.</p>

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Design, synthesis, in-silico studies, anti-cancer and anti-inflammatory activities of novel camphor-derived thiocarbamates as HER-2/COX-2 dual inhibitors

  • 期刊论文

  • 发表日期：

    2026年2月18日

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  • Esraa H. Abd El-Azeem,
  • Wael A. A. Fadaly,
  • Sayed A. Ahmed,
  • Afrah E. Mohammed,
  • Tamer Nasr,
  • Khaled El-Adl,
  • Doaa A. Abdelrheem,
  • Hussein S. Mohamed

摘要

Selective dual inhibition of cyclooxygenase (COX-2) and HER-2 offers a novel approach for treating inflammation-driven malignancies. In this study, a series of camphor-derived thiocarbamates (S1–S10) was synthesized by condensing camphor thiosemicarbazone, functionalizing with chloroacetyl chloride, and subsequent nucleophilic derivatization to create diverse heterocyclic and aromatic structures. IR and NMR spectroscopy confirmed the designed frameworks. Molecular docking studies demonstrated higher affinity of compounds S1 and S2 for COX-2 (ΔG = − 106.82 and − 109.44 kcal/mol) and HER-2 (ΔG = − 99.45 and − 99.80 kcal/mol), with multiple stabilizing hydrogen bonds. Enzymatic assays showed potent COX-2 inhibition (IC50 = 0.814 and 0.757 µM) and high selectivity over COX-1, matching the reference drug celecoxib. Both S1 and S2 demonstrated strong cytotoxicity against MCF-7 breast cancer cells (IC50 = 2.70 and 2.60 µM), comparable to doxorubicin and superior to dasatinib. ADMET profiling indicated favorable absorption, metabolism, and safety properties. Overall, these results identify S1 and S2 as potent, drug-like dual COX-2/HER-2 inhibitors with broad anti-inflammatory/anticancer efficacy, supporting further preclinical evaluation as candidates for targeted therapy in inflammation-associated cancers.