There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules.

Great progress has been made in recent years to reduce the high level of suffering caused by malaria worldwide. Notably, the use of insecticide-treated mosquito nets for malaria prevention and the use of artemisinin-based combination therapy (ACT) for malaria treatment have made a significant impact. Nevertheless, the development of resistance to the past and present anti-malarial drugs highlights the need for continued research to stay one step ahead. New drugs are needed, particularly those with new mechanisms of action. Here the range of anti-malarial medicines developed over the years are reviewed, beginning with the discovery of quinine in the early 1800s, through to modern day ACT and the recently-approved tafenoquine. A number of new potential anti-malarial drugs currently in development are outlined, along with a description of the hit to lead campaign from which it originated. Finally, promising novel mechanisms of action for these and future anti-malarial medicines are outlined.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2724-z) contains supplementary material, which is available to authorized users.

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An open-source approach to the problem of producing an off-patent drug in enantiopure form serves as an example of how academic and industrial researchers can join forces to make new scientific discoveries that could have a huge impact on human health.

Since the advent of click chemistry in 2001, the 1,4-disubstituted triazole has become an increasingly common motif in chemical sensors. Although these click-derived triazoles are generally used as a convenient method of ligation, their prevalence in chemosensors can be attributed to their ability to bind both cations and anions. In this critical review, we present an overview of the wide range of chemosensors that contain click-derived triazoles, with a particular focus on those cases where the triazole plays a functional, rather than merely a structural, role. Examples are categorised based on method of detection and key structural features, providing a complete picture of the current state of click-based chemosensors, as well as potential future directions for sensor design. (140 references).

We cover diverse methodologies, computational approaches, and case studies illustrating the ongoing efforts to develop viable drug candidates for treatment of COVID-19.

BackgroundPraziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill.Methodology/Principal FindingsWe have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself.Conclusions/SignificanceBoth resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.

A racemic mixture of R and S enantiomers of praziquantel (PZQ) is currently the treatment of choice for schistosomiasis. Though the S enantiomer and the metabolites are presumed to contribute only a little to the activity of the drug, in-depth sideby-side studies are lacking. The aim of this study was to investigate the in vitro activities of PZQ and its main metabolites, namely, R-and S-cis-and R-and S-trans-4=-hydroxypraziquantel, against adult worms and newly transformed schistosomula (NTS). Additionally, we explored the in vivo activity and hepatic shift (i.e., the migration of the worms to the liver) produced by each PZQ enantiomer in mice. Fifty percent inhibitory concentrations of R-PZQ, S-PZQ, and R-trans-and R-cis-4=-hydroxypraziquantel of 0.02, 5.85, 4.08, and 2.42 g/ml, respectively, for adult S. mansoni were determined in vitro. S-trans-and S-cis-4=-hydroxypraziquantel were not active at 100 g/ml. These results are consistent with microcalorimetry data and studies with NTS. In vivo, single 400-mg/kg oral doses of R-PZQ and S-PZQ achieved worm burden reductions of 100 and 19%, respectively. Moreover, worms treated in vivo with S-PZQ displayed an only transient hepatic shift and returned to the mesenteric veins within 24 h. Our data confirm that R-PZQ is the main effector molecule, while S-PZQ and the metabolites do not play a significant role in the antischistosomal properties of PZQ. S chistosomiasis or bilharzia is caused by blood flukes of the genus Schistosoma and is part of the group of neglected tropical diseases affecting more than 207 million people in tropical areas (1-3).The exclusive treatment to date for schistosomiasis is praziquantel (PZQ), which was discovered in the 1970s by Merck and Bayer. PZQ is administered as a racemic mixture of R and S enantiomers in tablets of 600 mg. The recommended dosage to treat schistosomiasis is 20 mg/kg three times in 1 day, and since PZQ does not act on juvenile worms, follow-up treatment 4 to 6 weeks later is strongly advised (4). In preventive chemotherapy programs, PZQ is administered as a single 40-mg/kg dose to at-risk populations (5). PZQ undergoes significant first-pass metabolism through the liver enzyme cytochrome P450 (CYP) 3A4 and to a lesser extent through 1A2 and 2C19 (6). R-PZQ is metabolized at a much higher rate than S-PZQ. R-PZQ is transformed mainly into cis-and trans-hydroxypraziquantel (4-OH-PZQ), while S-PZQ is converted to other monohydroxylated metabolites. In rat liver microsomes, the main metabolite is cis-4-OH-PZQ (7, 8), while in humans it is trans-4-OH-PZQ (9).The difference in the antischistosomal activity of each PZQ enantiomer has been known since 1983 (10), and several studies have observed greater activity of R-PZQ than of S-PZQ in vitro and in vivo (11)(12)(13). A clinical trial with Schistosoma japonicuminfected patients also recorded a higher efficacy of R-PZQ than of racemic PZQ at the same dosage (14, 15). Additionally, treatment with R-PZQ resulted in fewer adverse events than the standard treatment (14). However, ...