Biological activity of SAD-2: a novel original STING pathway activator

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Abstract
BACKGROUND: STING pathway activators with targeted delivery to tumor nodules are a promising option in cancer immunotherapy, especially as immunoconjugates. Existing compounds, such as MSA-2, are insufficiently effective as active immunoconjugate components, necessitating the development of new, more active compounds. AIM: The work aimed to examine the biological activity of the new compound SAD-2 and assess its potential as a new immunobiological drug for cancer therapy. METHODS: The work used contemporary methods of fine organic synthesis and analysis of the resulting compounds. MSA-2 was obtained from veratrole by multistage synthesis. SAD-2 was synthesized from MSA-2 by esterification with isopropyl alcohol in the presence of thionyl chloride. The antiproliferative activity of the compounds was assessed by the MTT method using colorectal cancer cell lines and human peripheral blood mononuclear cells. The induction of the interferon beta gene was assessed by real-time polymerase chain reaction using the human monocytic cell line THP-1. RESULTS: The new compound SAD-2 had 200–500 times higher antiproliferative activity according to IC50 than the existing compound MSA-2. Both MSA-2 and SAD-2 are active only in the presence of immune cells. SAD-2 showed 5–60 times higher relative induction of the IFNB1 gene than MSA-2, depending on the incubation time. CONCLUSION: SAD-2 is a promising new compound for developing immunoconjugates for targeted STING pathway activation in tumor nodules.

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