Search

International audience; Antimicrobial resistance (AMR) is a major public health issue, causing 5 million deaths per year. Without any action plan, AMR will be in a near future the leading cause of death ahead of cancer. AMR comes from the ability of bacteria to rapidly develop and share resistance mechanisms towards current antibiotics, rendering them less effective. To circumvent this issue and avoid the phenomenon of cross-resistance, new antibiotics acting on novel targets or with new modes of action are required. Today, the pipeline of potential new treatments with these characteristics includes promising compounds such as gepotidacin, zoliflodacin, ibezapolstat, MGB-BP-3, CRS-3123, afabicin and TXA-709, which are currently in clinical trials, and lefamulin, which has been recently approved by FDA and EMA. In this review, we report the chemical synthesis, mode of action, structure-activity relationships, in vitro and in vivo activities as well as clinical data of these eight small molecules listed above.

Cancer cells reprogram their metabolism to support their growth. Since the discovery of the Warburg effect, several other metabolic alterations and metabolites have been described in cancer cells, including lactate, glutamine and lipid metabolism reprogramming. Together these alterations provide rapidly dividing tumor cells with metabolic intermediates needed for nucleotide, protein and fatty acid biosynthesis. MicroRNAs are a class of small non-coding RNAs involved in the regulation of virtually all biological pathways. Altered microRNA expression patterns are associated with the onset and development of several diseases, including cancer. Tumor suppressor microRNAs targeting molecules involved in tumor metabolism are frequently downregulated in cancers. Therefore, microRNAs can serve as potential tumor biomarkers and also represent interesting therapeutic targets. This review summarizes recent findings about microRNAs involved in the regulation of tumor metabolism.

Sesquiterpene lactones (STLs) are a large group of terpenoids most commonly found in plants of the Asteraceae family, e. g. in chicory plants, displaying a wide range of interesting biological activities. However, further studies on the biological potential of chicory derived STLs and analogues are challenging as only four of these molecules are commercially available (as analytical standards), and to date there are no published or patented simple extraction-purification processes capable of large scale STLs isolation. In this work we describe a novel three-step large scale extraction and purification method for the simultaneous purification of 11,13-dihydrolactucin (DHLc) and lactucin (Lc) starting from a chicory genotype rich in these STLs and in the corresponding glycosyl and oxalyl conjugated forms. After a small-scale screening on 100 mg of freeze-dried chicory root powder, the best results were achieved with a 17 h water maceration at 30°C. With these conditions we managed to increase the content of DHLc and Lc, at the same time favouring the hydrolysis of their conjugated forms. On a larger scale, the extraction of 750 g of freeze-dried chicory root powder, followed by a liquid-liquid extraction step and a reversed-phase chromatography, allowed the recovery of 642.3 ± 76.3 mg of DHLc and 175.3 ± 32.9 mg of Lc. The two pure STLs were subsequently used in the context of semi-synthesis to generate analogues for biological evaluation as antibacterial agents. In addition, other described chicory STLs that are not commercially available were also synthesized or extracted to serve as analytical standards for the study. In particular, lactucin-oxalate and 11,13-dihydrolactucin-oxalate were synthesized in two steps starting from Lc and DHLc, respectively. On the other hand, 11β,13-dihydrolactucin-glycoside was obtained after a MeOH/H2O (70/30) extraction, followed by a liquid-liquid extraction step and a reversed-phase chromatography. Together, this work will help facilitate the evaluation of the biological potential of chicory derived STLs and their semisynthetic analogues.

Testo della relazione svolta al convegno INSEGNARE DIRITTO PENALE E PROCEDURA PENALE OGGI. CHE COSA, PERCHè, COME, svolltosi a Como il 5 ottobre 2018.

International audience