Diruthenium Diacetate Catalysed Aerobic Oxidation of Hydroxylamines and Improved Chemoselectivity by Immobilisation to Lysozyme

A new green method for the preparation of nitrones through the aerobic oxidation of the corresponding N,N-disubstituted hydroxylamines has been developed upon exploring the catalytic activity of a diruthenium catalyst, that is, [Ru2(OAc)4Cl]), in aqueous or alcoholic solution under mild reaction conditions (0.1 to 1 mol % catalyst, air, 50 °C) and reasonable reaction times. Notably, the catalytic activity of the dimetallic centre is retained after its binding to the small protein lysozyme. Interestingly, this new artificial metalloenzyme conferred complete chemoselectivity to the oxidation of cyclic hydroxylamines, in contrast to the diruthenium catalyst

New synthesis and biological evaluation of uniflorine A derivatives: Towards specific insect trehalase inhibitors

7-Deoxy-uniflorine A (6), synthesized ex novo with a straightforward and simple strategy, and the analogues 4, 5 and 7, were evaluated as potential inhibitors of insect trehalase from Chironomus riparius and Spodoptera littoralis. All the compounds were tested against porcine trehalase as the mammalian counterpart and \u3b1-amylase from human saliva as a relevant glucolytic enzyme. The aim of this work is the identification of the simplest pyrrolizidine structure necessary to impart selective insect trehalase inhibition, in order to identify new specific inhibitors that can be easily synthesized compared to our previous reports with the potential to act as non-toxic insecticides and/or fungicides. All the derivatives 4\u20137 proved to be active (from low micromolar to high nanomolar range activity) towards insect trehalases, while no activity was observed against \u3b1-amylase. In particular, the natural compound uniflorine A and its 7-deoxy analogue were found to selectively inhibit insect trehalases, as they are inactive towards the mammalian enzyme. The effect of compound 6 was also analyzed in preliminary in vivo experiments. These new findings allow the identification of natural uniflorine A and its 7-deoxy analogue as the most promising inhibitors among a series of pyrrolizidine derivatives for future development in the agrochemical field, and the investigation also outlined the importance of the stereochemistry at C-6 of pyrrolizidine nucleus to confer such enzyme specificity

Guselkumab for the treatment of psoriasis: a 60-week real-life multicenter retrospective experience

Background: Real-world data for guselkumab, the first interleukin-23 inhibitor approved to treat moderate-to-severe psoriasis, are scarce. This study represents the first 60-week, real-life, multicenter, retrospective experience to investigate the effectiveness, safety, tolerability, and drug retention of guselkumab in psoriatic patients. Research design and methods: Clinical information was collected at baseline and at weeks 12, 24, 36, 48, and 60. Results: The mean baseline Psoriasis Activity Severity Index (PASI) reduced from 14.2 to 3.1 at week 12 and decreased to around 0 at weeks 36, 48, and 60. PASI 75, PASI 90, and PASI 100 were 100%, 96.8%, and 83.9% at week 60, respectively. Multiple logistic regression analysis showed that neither body mass index >30, smoking, ≥3 comorbidities, difficult-to-treat areas, nor a failure to ≥2 prior biologic treatments significantly influenced PASI reduction (p > 0.05). Conclusions: Our findings confirm guselkumab as an appropriate therapeutic option in routine clinical practice, especially when dealing with complex patients with comorbidities or previous failure to biologic treatments

Use of apremilast in the psoriasis treatment: a real-life multicentre Italian experience

Background: Apremilast is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicentre real-world setting. Methods: We retrospectively reviewed data from all psoriatic patients who received at least one dose of apremilast, collecting demographic data and medical history, at baseline and periodically until 36 months. Results: A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months, significantly shorter when comorbidities were≥3 and if biologic drugs were previously administered.ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4;the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive apremilast.At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure(19%) or secondary failure(6.3%). Conclusions: Apremilast proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favourable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival