ABSTRACT
Novel coronavirus 2019 (COVID-19) has been one of the largest and most devastating global pandemics of our time. There have been several complications of this disease that have also proven to be debilitating and deadly. While primarily affecting the respiratory system, some cases presented with uncommon complications such as pneumopericardium and spontaneous pneumothorax. We present a case of an elderly female diagnosed with COVID-19 found to have both spontaneous pneumothorax and pneumopericardium. She had a complicated hospital course and ultimately succumbed to her illness. While the pathogenesis of these conditions is not yet fully understood, further studies are needed to help clinicians develop treatment and prevention strategies to improve patient outcomes.
ABSTRACT
Emergence of drug resistant Plasmodium falciparum including artemisinin-tolerant parasites highlights the need for new antimalarials. We have previously shown that dibemequines, 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side chains, are efficacious. In this study, analogues in which the terminal phenyl group of the dibemethin was replaced with a 2-pyridyl group and in which the 4-amino-7-chloroquinoline was either maintained or replaced with a 4-aminoquinoline-7-carbonitrile were synthesized in an effort to improve druglikeness. These compounds exhibited significantly improved solubility and decreased lipophilicity and were potent against chloroquine-sensitive (NF54) and -resistant (Dd2 and 7G8) P. falciparum strains with 5/6 having IC50 < 100 nM against the NF54 strain. All inhibited both ß-hematin (synthetic hemozoin) formation and hemozoin formation in the parasite. Parasitemia was reduced by over 90% in P. berghei infected mice in 3/6 derivatives following oral dosing at 4 × 30 mg/kg, with microsomal metabolic stability data suggesting that this could be attributed to highly active metabolites.
