Design, Synthesis, and Testing of 1,2,3-Triazolo-Quinobenzothiazine Hybrids for Cytotoxic and Immunomodulatory Activity.

Phenothiazines, mainly known for their antipsychotic activity, have recently attracted attention as potential compounds with anticancer and immunomodulatory activity In this study, 20 new quinobenzothiazines (MJ1-MJ20) were synthesized and their effects on normal cell lines (BEAS-2B, NHDF) and cancer cell lines (HCT116, MCF7, A549, SH-SY5Y, U2OS) were investigated. The studies included cytotoxicity assessment, analysis of the expression of genes (BCL2, AIFM2, MDM2) and pro-inflammatory cytokines (IL6, IL8) using the RT-qPCR method, and prediction of biological activity using the PASS platform. The results indicate that the compounds MJ19 and MJ20 have the greatest effect on the induction of pro-inflammatory (IL6, IL8) and antiapoptotic (BCL2, MDM2) genes, suggesting their potential use in therapies for inflammatory and autoimmune diseases. Gene expression analysis showed that compound MJ2 in BEAS-2B cells significantly induced the expression of AIFM2, a protein responsible for protecting against ferroptosis, while moderately increasing the expression of BCL2 and MDM2, suggesting a potential role for MJ2 in the modulation of protective mechanisms of healthy cells, e.g., avoiding apoptosis death. These results emphasize the potential of quinobenzothiazines as multifunctional bioactive compounds, which require further studies to determine their mechanisms of action and specificity.