Comprehensive investigation of biological activities and pharmacological properties of new indole-artesunate hybrid molecules

Cancer is one of the leading causes of death worldwide and its incidence is increasing worldwide. Therefore, the need for the development of powerful pharmaceuticals for cancer treatment is also increasing. In this study, it was aimed to comprehensively investigate the biological and pharmacological properties of 11 indole-artesunate hybrid molecules obtained by combining the indole ring and artesunate substance. In this direction, the antioxidant potentials of the compounds were tested with five different methods (DPPH, ABTS, Galvinoxyl, Phosphomolybdenum and FRAP). The cytotoxic properties of the compounds in different cancer cell lines and a healthy cell line were determined by the MTT method. The colony formation and invasion capacities, wound healing potentials and apoptotic effects of the compounds with determined cytotoxic potentials on cancer cells and their effects on mRNA expression of genes in the apoptotic pathway were investigated. As a result of the study, antioxidant capacities of compounds were not determined in other antioxidant capacity methods except phosphomolybdenum method. It was determined that eight of the compounds whose cytotoxic properties were tested with MTT method were effective in various cell lines. In Ishikawa cell line, EC50 values of D1 and D6 compounds (20.22 μM and 22.90 μM) were very close to EC50 value of paclitaxel substance (19.3 μM) used as positive control. In HepG2 cell line, EC50 values of D1 and D2 compounds (5.43 μM, 5.63 μM) were very close to EC50 value of paclitaxel substance (4.5 μM) used as positive control and D3 compound (2.75 μM) exhibited better activity than positive control. Colony formation potentials of compounds tested; It was determined that it generally prevented colony formation by more than 90% compared to the control group. It was tested that D1 and D2 compounds, whose invasion properties were investigated, significantly inhibited invasion in HepG2, Ht-29 and Panc-1 cancer cell lines. It was seen that all substances tested in the wound healing method inhibited cell migration compared to the control group. It was determined that the compounds induced apoptosis as a result of both the Annexin-V/PI method and the analysis of mRNA expressions of genes in the apoptotic pathway with Real-Time PCR. Considering all these results, one or more compounds used in this study have the potential to become cancer drugs with further studies. Therefore, detailed analyses of the compounds used in the study should be performed in in vitro and in vivo applications.