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Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively.

Abstract Background Preoperative antibiotic prophylaxis is essential for preventing surgical site infection (SSI). The aim of this study was to evaluate compliance with international and local recommendations in caesarean deliveries carried out at the Obstetrics and Gynaecology Service of the Ambato General Hospital, as well as any related health and economic consequences. Methods A retrospective indication-prescription drug utilization study was conducted using data from caesarean deliveries occurred in 2018. A clinical pharmacist assessed guidelines compliance based on the following criteria: administration of antibiotic prophylaxis, antibiotic selection, dose, time of administration and duration. The relationship between the frequency of SSI and other variables, including guideline compliance, was analysed. The cost associated with the antibiotic used was compared with the theoretical cost considering total compliance with recommendations. Descriptive statistics, Odds Ratio and Pearson Chi Square were used for data analysis by IBM SPSS Statistics version 25. Results The study included 814 patients with an average age of 30.87 ± 5.50 years old. Among the caesarean sections, 68.67% were emergency interventions; 3.44% lasted longer than four hours and in 0.25% of the deliveries blood loss was greater than 1.5 L. Only 69.90% of patients received preoperative antibiotic prophylaxis; however, 100% received postoperative antibiotic treatment despite disagreement with guideline recommendations (duration: 6.75 ± 1.39 days). The use of antibiotic prophylaxis was more frequent in scheduled than in emergency caesarean sections (OR = 2.79, P = 0.000). Nevertheless, the timing of administration, antibiotic selection and dose were more closely adhered to guideline recommendations. The incidence of surgical site infection was 1.35%, but tended to increase in patients who had not received preoperative antibiotic prophylaxis (OR = 1.33, P = 0.649). Also, a significant relationship was found between SSI and patient age (χ2 = 8.08, P = 0.036). The mean expenditure on antibiotics per patient was 5.7 times greater than that the cost derived from compliance with international recommendations. Conclusions Surgical antibiotic prophylaxis compliance was far below guideline recommendations, especially with respect to implementation and duration. This not only poses a risk to patients but leads to unnecessary expenditure on medicines. Therefore, this justifies the need for educational interventions and the implementation of institutional protocols involving pharmacists.

Applications for pharmacogenomics in pharmacy practice: A scoping review Hayashi M, Hamdy DA, Mahmoud SH. Research in Social and Administrative Pharmacy 2021. Article in press. https://doi.org/10.1016/j.sapharm.2021.08.009 Roles, barriers and behavioral determinants related to community pharmacists' involvement in optimizing opioid therapy for chronic pain: a qualitative study Alenezi A, Yahyouche A, Paudyal V. International Journal of Clinical Pharmacy. 2021. https://doi.org/10.1007/s11096-021-01331-1 Ability to detect potentially inappropriate prescribing in older patients: comparative analysis between PIM‑Check and STOPP/STARTv2 Farhat A, Panchaud A, Al‑Hajje A, Al‑Hajje PO, Csajka C. European Journal of Clinical Pharmacology. 2021, 77:1747-1756 https://doi.org/10.1007/s00228-021-03171-4

Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds. This report shows the antileishmanial effect of several series of compounds (53), derived from podophyllotoxin (a natural cyclolignan isolated from rhizomes of Podophyllum spp.) and podophyllic aldehyde, on a transgenic, fluorescence-emitting strain of Leishmania infantum. These compounds were tested on both promastigotes and amastigote-infected mouse splenocytes, and in mammalian – mouse non-infected splenocytes and liver HepG2 cells – in order to determine selective indexes of the drugs. Results obtained with podophyllotoxin derivatives showed that the hydroxyl group at position C-7α was a structural requisite to kill the parasites. On regards podophyllic aldehyde, derivatives with C9-aldehyde group integrated into a bicyclic heterostructure displayed more potent antileishmanial effects and were relatively safe for host cells. Docking studies of podophyllotoxin and podophyllic aldehyde derivatives showed that these compounds share a similar pattern of interaction at the colchicine site of Leishmania tubulin, thus pointing to a common mechanism of action. However, the results obtained suggested that despite tubulin is a remarkable target against leishmaniasis, there is a poor correlation between inhibition of tubulin polymerization and antileishmanial effect of many of the compounds tested, fact that points to alternative pathways to kill the parasites. Keywords: Leishmania, Tubulin, DNA-Topoisomerase, Podophyllotoxin, Podophyllic aldehyde