Determination of biological activities of new generation Alkenyl-benzothiophene derivatives

Cancer remains a major health challenge, and the acquisition of resistance by cancer cells to current therapies further complicates treatment strategies. Therefore, the development of effective and innovative anticancer agents is of critical importance. Heterocyclic compounds, particularly sulfur-containing benzothiophene derivatives, have emerged as promising scaffolds in drug design due to their diverse biological activities. In this study, the biological properties of novel alkenyl benzothiophene derivatives synthesized via the Sonogashira reaction were comprehensively investigated. Cytotoxicity (MTT), cell migration, and wound-healing assays demonstrated that compounds Q37 and Q48 exerted significant antiproliferative and anti-invasive effects on cancer cells. Annexin V staining and qRT-PCR analyses revealed that these compounds effectively induced apoptosis by modulating the expression of BCL2, BAX, Caspase 3, Caspase 8, Caspase 9, and P53 genes. In LPS-stimulated RAW264.7 macrophages, compounds Q35, Q37, Q40, Q41, Q44, Q46, and Q49 markedly suppressed nitric oxide production and the expression of pro-inflammatory genes (TNF-α, COX-2, iNOS, IL-6), whereas Q42, Q48, and Q64 were found to enhance the inflammatory response. Additionally, certain compounds significantly increased IL-10 expression. Overall, these findings highlight the potent anticancer and anti-inflammatory potential of Q37 and Q48, indicating their promise for further preclinical and clinical investigations. This study provides valuable insights into the potential of benzothiophene derivatives as novel therapeutic candidates for cancer treatment.