Flexible 2,4-diaminopyrimidine bearing a butyrolactone as Plasmodium falciparum dihydrofolate reductase inhibitors.

Recently, P218, a new flexible antifolate targeting Plasmodium falciparum dihydrofolate reductase (PfDHFR), has entered its clinical trial with good safety profile and effective Pf infection prevention. However, it carries a free carboxyl terminal, which is hydrophilic and prone to metabolic glucuronidation. Here, a new series of P218 analogues carrying butyrolactone has been synthesized with the purpose of enhancing lipophilicity and minimizing metabolic instability.

Characterizing a visual lateral flow device for rapid SARS-CoV-2 virus protein detection: pre-clinical and system assessment.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have affected more than 769 million individuals worldwide over the last few years. Although the pandemic is transitioning into an endemic, the COVID-19 outbreak is still a global concern. A rapid screening platform is needed for effective preventive and control measures.

Discovery of rigid biphenyl DHFR inhibitors using a fragment linking strategy.

dihydrofolate reductase (DHFR), a historical target for antimalarials, has been considered compromised due to resistance inducing mutations caused by pyrimethamine () overexposure. The clinical candidate has demonstrated that inhibitors could efficiently target both -sensitive and -resistant parasites through careful drug design. Yet, clinical development has been limited by its pharmacokinetic profile, incompatible with single dose regimen.