Synthesis of Bio-Inspired 1,3-Diarylpropene Derivatives via Heck Cross-Coupling and Cytotoxic Evaluation on Breast Cancer Cells

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 17; p. 5373
• Main Authors: Tan, Aik Sian, Singh, Jaymeer, Rezali, Nurul Syafiqah, Muhamad, Musthahimah, Nik Mohamed Kamal, Nik Nur Syazni, Six, Yvan, Azmi, Mohamad Nurul
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.08.2022; MDPI
• Subjects: 1,3-diarylpropene; Antineoplastic Agents - pharmacology; Breast cancer; breast cancer cells; Breast Neoplasms - drug therapy; Cancer; Carbon; Cell Line, Tumor; Cell Proliferation; Chemical reactions; Chemical Sciences; Cross coupling; cytotoxic effects; Cytotoxicity; Drug Screening Assays, Antitumor; Eugenol; Female; Heck cross-coupling; Humans; Isomers; Life Sciences; MCF-7 Cells; Medicinal Chemistry; Palladium; Palladium - chemistry; Palladium - pharmacology; Reaction products; Stereoselectivity; Structure-Activity Relationship; Substitution reactions; Tamoxifen - pharmacology; Toxicity; β-hydride elimination; Massachusetts; Malaysia; 1,3-diarylpropene; breast cancer cells; Heck cross-coupling; β-hydride elimination; cytotoxic effects; 1 3-diarylpropene; beta-hydride elimination
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27175373

The Heck cross-coupling reaction is a well-established chemical tool for the synthesis of unsaturated compounds by formation of a new C-C bond. In this study, 1,3-diarylpropene derivatives, designed as structural analogues of stilbenoids and dihydrostilbenoids, were synthesised by the palladium-catalysed reactions of 2-amidoiodobenzene derivatives with either estragole or eugenol. The products were obtained with high (E) stereoselectivity but as two regioisomers. The ratios of isomers were found to be dependent on the nature of the allylbenzene partner and were rationalised by electronic effects exercising a determining influence in the β-hydride elimination step. In addition, the cytotoxic effects of all the Heck reaction products were evaluated against MCF-7 and MDA-MB-231 human breast cancer cells, with unpromising results. Among all, compound 7d exhibited weak cytotoxic activity towards MCF-7 cell lines with IC50 values of 47.92 µM in comparison with tamoxifen and was considered to have general toxicity (SI value < 2).