New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors

Abstract

A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic acids and rosmaricine, has been synthesized and their ability to inhibit both STAT3 and NF-κB transcription factors have been evaluated. Results showed that most of the new hybrid compounds were able to strongly and selectively bind to STAT3, whereas the parent drugs were devoid of this ability at the tested concentrations. Some of them were also able to inhibit the NF-κB transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-κB inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents.

Cinnamic acid decreases periodontal inflammation and alveolar bone loss in experimental periodontitis

“…28 The derivatives of cinnamic acid include p-coumaric, and caffeic acids exhibited significant efficacy in terms of preventing osteoclastic activity and promoting osteoblastic activity. 11,17,[29][30][31][32] Besides, one of the most common antioxidant supplements, propolis, is also rich in cinnamic acid content and was reported to block NF-κB and MAPK activation in macrophage cells. 11 Gabriele et al also…”

“…showed inhibition of NF-κB transcription factors with cinnamic acid derivatives. 17 Schink et al reported that cinnamic acid reduced the phosphorylation of Akt and IKB-α along with decreased IL-8 expressions. 33 Decreased levels of pro-inflammatory cytokines TNFα, IL-1β, and IL-18 and neutrophil infiltration and apoptosis in mice were also demonstrated in another study.…”

“…15,16 Recently, Gabriele et al found that cinnamic acid derivatives selectively inhibited NF-κB transcriptional activity. 17 Besides, Ruan et al demonstrated that cinnamic ester hybrid molecules suppressed nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase (COX)-2 through NF-κB signaling pathway. 16 Song et al also reported decreased pro-inflammatory cytokine levels such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α and NO production.…”

“…19 Based on the reports of the previous studies, the present study hypothesized that the anti-inflammatory effects of cinnamic acid and derivatives might also be beneficial in preventing periodontal inflammation and alveolar bone loss caused by periodontitis. 16,17,19 Therefore, the aim of the present study was to evaluate the effects of cinnamic acid administered by two different forms on an experimental periodontitis model in Wistar rats. The tissue expressions of PPAR-γ, COX-2, RANKL, and OPG, along with the inflammatory cell infiltration, osteoblast, and osteoclast cell counts, were determined.…”

Systematic analysis of gene expression alterations and clinical outcomes of STAT3 in cancer

“…STAT homologs in mammals are comprised of six conserved structural domains, as follows: N-domain (ND), coiled-coil, DNA binding, linker, Src homology 2 (SH2), and transcriptional activation domain [ 31 , 32 ]. Under normal physiological conditions, the activation of STATs is strictly regulated, which could regulate cell proliferation, survival and other critical cellular functions by modulating the expression of specific target genes.…”