Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. However, there is a growing demand for novel small-molecule IFN inducer due to tolerance, toxicity, or short duration of action following direct administration of IFNs. In this study, we assessed arylpiperazine (ARP) as a new core skeleton of IFN inducer. To investigate structure–activity relationship, we designed and synthesized a series of ARP analogues and evaluated the ability to stimulate IFN response in THP-1 human monocyte cells. Compound 5i was identified as a potent type I IFN inducer as it significantly increased cytokine secretion and increased expression of various IFN-stimulating genes which are representative biomarkers of type I IFN pathway. Our results suggested a beneficial therapeutic potential of 5i as an anti-viral agent.
This study was financially supported by Korea Institute of Science and Technology (KIST) Institutional Program (2E30180) and Bio & Medical Technology Development Program (NRF-2019M3E5D4066905) of the National Research Foundation funded by Korean government (MSIT), a grant from Priority Research Centers Program (2019R1A6A1A11051471), 2020R1C1C1010044 funded by the National Research Foundation of Korea (NRF) and Convergence brain research through cross-institute collaboration (KBRI 20-BR-03-01/ IBS-R001-D1-2020-b02).This study was financially supported by Korea Institute of Science and Technology (KIST) Institutional Program (2E30180) and Bio & Medical Technology Development Program (NRF-2019M3E5D4066905) of the National Research Foundation funded by Korean government (MSIT), a grant from Priority Research Centers Program (2019R1A6A1A11051471), 2020R1C1C1010044 funded by the National Research Foundation of Korea (NRF) and Convergence brain research through cross-institute collaboration (KBRI 20-BR-03-01/ IBS-R001-D1-2020-b02).
