ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

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

Chemistry of Medicinal and Aromatic Plants Department, Research Institute of Medicinal and Aromatic Plants (RIMAB), Beni-Suef University, Beni-Suef, Egypt

E-mail: Hussein.shaban@rimp.bsu.edu.eg

Received: 27 November 2025  Accepted: 23 January 2026

Abstract:

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.

Keywords: Camphor; Tyrosine kinase; Anti-cancer; Anti-inflammatory; COX-2/HER-2 inhibition; Docking; ADMET

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04699-4

Chemical Papers 80 (4) 4373–4389 (2026)