Determining the anti-carcinogenic and anti-inflammatory effects of novel Benzothiophene derivatives

Heterocyclic compounds play an important role in drug discovery and development. Benzothiophenes are sulfur-containing heterocyclic compounds. These compounds are involved in the basic structural skeletons of many basic natural and synthetic compounds benzothiophene and benzothiophene-based compounds exhibit various biological activities such as anti-microbial, anti-cancer, anti-anti-angiogenic, anti-inflammatory, anti-oxidant. This study investigated the cytotoxicity, apoptosis, and anti-inflammatory effects of benzothiophene compounds. The A549, LnCaP, and MCF-7 cell line were used to determine the cytotoxicity and apoptosis effects of the compounds, and healthy embryonic cell lines (HEK293) were used as controls. Compounds giving EC50 were used in these cell lines, apoptosis analysis was performed by Annexin FITC/PI staining and mRNA was isolated and qRT-PCR usued to measure the levels of apoptosis-related genes (Bax, Bcl2, Casp3, Casp8 and Casp9). In addition, the LPS stimulated RAW264.7 cell line was used to reveal the anti-inflammatory effects of the compounds and nitric oxide formed was determined by the Griess method. The expression levels of genes involved in inflammation were evaluated using qRT-PCR. According to the results, AD3 and AD5 compounds did not have significant cytotoxic effects in cancer cell lines (A549, LnCaP and MCF-7), however AD1, AD7, and AD3S1 compounds showed good cytotoxicity, and induced apoptosis by activating Bax, Casp3, Casp8, and Casp9 genes. Additionally, it has been discovered that the compounds AD1, AD3, AD5, AD7, and AD3S1 inhibit proinflammatory genes (TNF-a, COX-2, iNOS, and IL-6) while promoting the anti-inflammatory gene (IL-10). In conclusion, benzothiophene derivatives will play an important role in the design and synthesis of promising drugs for lung cancer, prostate cancer and breast cancer treatments and may have potential as anti-inflammatory drugs.