Determination of anticancer and antiinflammatory properties of 3-aryl/alkyl-(2-aryl)-benzo[b]thiophene derivatives

Cancer remains one of the leading global health challenges due to its biological diversity, molecular complexity, and resistance to treatment. The limited efficacy and systemic toxicity of conventional therapies have necessitated the development of novel, targeted therapeutic agents. In this context, molecules capable of modulating intracellular signaling pathways and suppressing inflammatory responses have gained prominence. Benzothiophene-based compounds, in particular, have emerged as promising candidates due to their ability to induce apoptosis and regulate inflammation at the molecular level. Structurally enriched with aryl and alkyl substituents, these derivatives exhibit enhanced binding affinity to biological targets and significantly improved anticancer and anti-inflammatory activities. This thesis investigates the cytotoxic and anti-inflammatory effects of five organosynthetic benzothiophene derivatives (AD6, AD8, AD10, AD11, AD12) modified with aryl and alkyl groups. MTT assays were performed on various human cancer cell lines (MCF-7, Caco-2, HepG2, LNCaP), revealing selective cytotoxic activity for AD8 and AD10. AD8 showed significant effects across four cell lines, with EC₅₀ values ranging from 145 to 192 µM, while AD10 demonstrated activity in three cell lines, with EC₅₀ values between 146 and 225 µM. No toxicity was observed in the healthy HEK293 cell line. Flow cytometry analysis indicated strong apoptotic effects of AD10 in HepG2 (89.99%) and LNCaP (64.15%) cells, while AD8 induced moderate apoptosis in HepG2 (44.93%). In Caco-2 and MCF-7 cells, both compounds exhibited limited apoptotic activity comparable to paclitaxel. Real-time PCR analysis revealed upregulation of BAX, CASP3, CASP8, CASP9, and P53 gene expression. The anti-inflammatory potential was evaluated in RAW264.7 murine macrophage cells, with no toxicity observed at low doses. In the Griess assay, AD10 showed the highest effect by suppressing nitric oxide (NO) production by 54.78% at 62 µM. Other compounds also demonstrated significant NO inhibition. qPCR analysis confirmed the downregulation of pro-inflammatory genes and upregulation of IL-10 expression. The results indicate that AD10 stands out with its potent apoptotic and anti-inflammatory effects, while AD8 presents a balanced biological profile.