Polymerization of the cytosolic protein actin is critical to cell movement and host-cell invasion by the malaria parasite, Plasmodium falciparum. Any disruption to actin polymerization dynamics will render the parasite incapable of invading a host cell and thereby unable to cause infection. Here, we explore the potential of using truncated latrunculins as potential chemotherapeutics for the treatment of malaria. Exploration of the binding interactions of the natural actin inhibitor latrunculins, with actin revealed how a truncated core of the inhibitor could retain its key interaction features with actin. This truncated core was synthesised and subjected to preliminary structure-activity relationship studies to generate a focused set of analogues. Biochemical analyses of these analogues demonstrate their 6-fold increased activity compared with latrunculin B against Plasmodium falciparum and a 16-fold improved selectivity ex vivo. These data establish the latrunculin core as a potential focus for future structure-based drug design of chemotherapeutics against malaria.
Sulfamethoxazole/Trimethoprim (SMX/TMP) is a commonly used antibiotic, its' known adverse reaction of hepatotoxicity leading to acute liver failure is considered rare. We present a case of a 22 year old female who developed jaundice and acute liver failure one week after taking SMX/TMP for a UTI. After an extensive work up, a clinical diagnosis of SMX/TMP induced liver failure was reached. Over the course of several weeks she made a good clinical and biochemical recovery with supportive care. In this case report we describe her clinical presentation and course, and present a brief review of the literature.
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