Sudan and South Sudan ::From One to Two /

The Republic of Sudan's former Culture Minister and a leading architect in the movement to gain independence for South Sudan, Bona Malwal, provides a factual and personal account of the break up of Sudan. He explores its troubled history post-colonialism and offers a frank account of the many challenges that both nations face in the coming years

Anti-Parasitics with a Triple Threat: Targeting Parasite Enzymes, the Proton Motive Force, and Host Cell-Mediated Killing

We investigated the effects of the tuberculosis drug candidate SQ109 (8a) and of its analog MeSQ109 (8b) against Leishmania mexicana in promastigote and amastigote forms and against host cell macrophages finding potent activity (1.7 nM) for MeSQ109 against the intracellular forms, as well as low toxicity (∼61 μM) to host cells, resulting in a selectivity index of ∼36,000. We then investigated the mechanism of action of MeSQ109, finding that it targeted parasite mitochondria, collapsing the proton motive force, as well as targeting acidocalcisomes, rapidly increasing the intracellular Ca2+ concentration. Using an E. coli inverted membrane vesicle assay, we investigated the pH gradient collapse for SQ109 and 17 analogs, finding that there was a significant correlation (on average, R = 0.67, p = 0.008) between pH gradient collapse and cell growth inhibition in Trypanosoma brucei, T. cruzi, L. donovani, and Plasmodium falciparum. We also investigated pH gradient collapse with other antileishmanial agents: azoles, antimonials, benzofurans, amphotericin B, and miltefosine. The enhanced activity against intracellular trypanosomatids is seen with Leishmania spp. grown in macrophages but not with Trypanosoma cruzi in epithelial cells and is proposed to be due in part to host-based killing, based on the recent observation that SQ109 is known to convert macrophages to a pro-inflammatory (M1) phenotype. © 2025 American Chemical Society