Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Chu, Yeonjeong^1,2  Reddy, B. Raja Sekhara³  Gajulapalli, V. Pratap Reddy²  Babu, K. Sudhakar³  Kim, Eunha²  Lee, Sanghee^1,4 

[1] Korea Inst Sci & Technol, Brain Sci Inst, Seoul, South Korea

[2] Ajou Univ, Dept Mol Sci & Technol, Suwon, South Korea

[3] Sri Krishnadevaraya Univ, Dept Chem, Anantapur, Andhra Pradesh, India

[4] Hanyang Univ, Dept HY KIST Bioconvergence, Seoul, South Korea

关键词: Interferon inducer;    type I Interferon;    Arylpiperazine;    Anti-viral agent;    Innate immunity;   

DOI  :  10.1016/j.bmcl.2020.127613

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free