Two series of novel hybrid heterocyclic compounds that combine the imidazole ring with bioactive piperidine, morpholine or piperazine heterosystems, through a hydrazone unit, were easily obtained by two competitive pathways. Starting from 5‐amino‐4‐cyanoformimidoyl imidazoles and 1‐aminopiperidine, 4‐aminomorpholine or 1‐amino‐4‐methylpiperazine under mild acidic media led to the selective synthesis of 5‐aminoimidazole 4‐carboxamidrazones, whereas the corresponding 4‐hydrazonoyl cyanide derivatives were obtained under stronger acidic conditions. These highly functionalized imidazoles provide convenient synthetic precursors to a vast array of heterocycles with potential pharmaceutical applications. The reaction mechanisms were elucidated on the basis of experimental assays and in silico calculations. The compounds were screened against colorectal cancer HCT116‐p53 wt cell line, and significant IC₅₀ values of 3.69 μM and 4.83 μM were obtained.

Solid-state fermentation (SSF) involves the growth of microorganisms on solid substrates, mimicking natural environments of many species. Due to sustainability concerns, transforming agro-industrial by-products into value-added products through SSF has been increasingly studied. Brewer’s spent grain (BSG), the main by-product of beer production, mostly consists of barley grain husks, making BSG a great support for microorganism cultivation. Although autoclaving remains the standard sterilization and pretreatment method of substrates, electric field technologies and their attendant ohmic heating (OH) have great potential as an alternative technology. In the present work, pretreatment of BSG by OH was explored in SSF with Aspergillus niger to produce commercially valuable enzymes. OH favored the solubilization of phenolic compounds, total protein, and reducing sugars significantly higher than autoclaving. SSF of treated BSG led to the production of lignocellulosic enzymes, with xylanases being the most active, reaching 540 U/g, a 1.5-fold increase in activity compared to autoclaved BSG. Protease activity was also improved 1.6-fold by OH, resulting in 49 U/g. Our findings suggest that OH treatment is an effective alternative to autoclaving and that its integration with SSF is a sustainable strategy to enhance by-product valorization through enzyme production with many industrial applications, according to circular economy guidelines.

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC₅₀ values between 1.4 and 7.5 μM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.

Solid-state fermentation (SSF) involves the growth of microorganisms on solid substrates, mimicking natural environments of many species. Due to sustainability concerns, transforming agro-industrial by-products into value-added products through SSF has been increasingly studied. Brewer’s spent grain (BSG), the main by-product of beer production, mostly consists of barley grain husks, making BSG a great support for microorganism cultivation. Although autoclaving remains the standard sterilization and pretreatment method of substrates, electric field technologies and its attendant ohmic heating (OH) have great potential as an alternative technology. In the present work, pretreatment of BSG by OH was explored in SSF with Aspergillus niger to produce commercially valuable enzymes. OH favored the solubilization of phenolic compounds, total protein and reducing sugars, significantly higher than autoclaving. SSF of treated BSG led to the production of lignocellulosic enzymes, with xylanases being the most active, reaching 540 U/g, a 1.5-fold increase in activity compared to autoclaved BSG. Protease activity was also improved 1.6-fold by OH, resulting in 49 U/g. Our findings suggest that OH treatment is an effective alternative to autoclaving and that its integration with SSF is a sustainable strategy to enhance by-products valorization through enzymes production with many industrial applications, according to circular economy guidelines.