We have evaluated the antischistosomal activity of synthetic dihydrobenzofuran neolignans (DBNs) derived from (±)-trans-dehydrodicoumaric acid dimethyl ester (1) and (±)-trans-dehydrodiferulic acid dimethyl ester (2) against adult Schistosoma mansoni worms in vitro. Compound 4 ((±)-trans-4-O-acetyldehydrodiferulic acid dimethyl ester) displayed the most promising activity; at 200 μm, it kills 100 ± 0% of worms after 24 h, which resembles the result achieved with praziquantel (positive control) at 1.56 μm. The hydrogenation of the double bond between C7' and C8', the introduction of an additional methyl group at C3', and a double bond between C7 and C8 decreased the schistosomicidal activity of DBNs. On the other hand, the presence of the acetoxy group at C4 played an interesting role in this activity. These results demonstrated the interesting schistosomicidal potential of DBNs, which could be further exploited.

Schistosoma mansoni adaptive success is related to regulation of replication, transcription and translation inside and outside the intermediate and definitive host. We hypothesize that S. mansoni alters its epigenetic state in response to the mammalian host immune system, reprogramming gene expression and altering the number of eggs. In response, a change in the DNA methylation profile of hepatocytes could occurs, modulating the extent of hepatic granuloma. To investigate this hypothesis, we used the EBi3 -/murine (Mus musculus) model of S. mansoni infection and evaluated changes in new and maintenance DNA methylation profiles in the liver after 55 days of infection. We evaluated expression of epigenetic genes and genes linked to histone deubiquitination in male and female S. mansoni worms. Comparing TET expression with DNMT expression indicated that DNA demethylation exceeds methylation in knockout infected and uninfected mice and in wild-type infected and uninfected mice. S. mansoni infection provokes activation of demethylation in EBi3 -/-I mice (knockout infected). EBi3 -/-C (knockout uninfected) mice present intrinsically higher DNA methylation than WTC (control uninfected) mice. EBi3 -/-I mice show decreased hepatic damage considering volume and reduced number of granulomas compared to WTI mice; the absence of IL27 and IL35 pathways decreases the Th1 response resulting in minor liver damage. S. mansoni males and females recovered from EBi3 -/-

Protein p53 is degraded by the 26S proteasome, a protein complex that breaks down cellular proteins. Degradation begins with activation of the protein ubiquitin (Ub) by the ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, and ubiquitin E3 ligases, linking Ub or the polyubiquitin chain to p53 and marking it for degradation by the 26S proteasome. E3 ubiquitin ligases participate in this process and regulate p53 stability. There are compounds that inhibit the 26S proteasome and interfere at the p53 level, and some of these inhibitors are used to treat cancer and other diseases and can stabilize tumor suppressor proteins through the p53 pathway. This review discusses how the ubiquitin–proteasome system, p53, and these compounds are related.

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