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BACKGROUND Despite the dynamic development of medicine, globally cancer diseases remain the second leading cause of death. Therefore, there is a strong necessity to improve chemotherapy regimens and search for new anticancer agents. Pyridocarbazoles are compounds with confirmed antitumor properties based on multimodal mechanisms, i.a. DNA intercalation and topoisomerase II-DNA complex inhibition. One of them, S16020, displayed a wide spectrum of activity. OBJECTIVE The aim of the study was to investigate the antitumor potency of six S16020 derivatives, synthesized according to the SAR (structure-activity relationship) method. METHODS The biological evaluation included influence on cancer cell viability, proliferation, and migration, as well as P-glycoprotein activity. NHDF, A549, MCF-7, LoVo, and LoVo/DX cell lines were used in the study. RESULTS All derivatives displayed low toxicity to normal (NHDF) cells at 1 and 2 µM (≤ 20% of cell growth inhibition). The highest reduction in cell viability was noted in A549 cells which was accompanied by significant disruption of cells proliferation and motility. Compound 1 exhibited the strongest cytotoxic, antiproliferative, and antimigratory effects, higher than the reference olivacine. A significant reduction in P-glycoprotein activity was found for derivatives 6 and 1. CONCLUSION S16020 derivatives could be considered as potential candidates for new anticancer drugs.