Novel Minor Groove Binders Cure Animal African Trypanosomiasis in an in Vivo Mouse Model

Abstract

Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa due to its huge impact on livestock health. Existing therapies including those based upon Minor Groove Binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places due to the emergence of resistant parasites. Consequently, the need for new

Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype

“…5 Although the full mechanism of antibacterial activity of these compounds has not yet been established, there is strong evidence that it is novel, involving the inhibition of several DNA-centric events. 6,7 These compounds were selected for development because of their potent antibacterial properties; however, they also possess activity against a number of other species, including various parasites. [7][8][9][10][11] This study is concerned with exploiting the anti-parasitic activity present within this panel of compounds.…”

“…6,7 These compounds were selected for development because of their potent antibacterial properties; however, they also possess activity against a number of other species, including various parasites. [7][8][9][10][11] This study is concerned with exploiting the anti-parasitic activity present within this panel of compounds. Activity against multiple organisms presents a potential issue as our S-MGBs in clinical development exert their antibacterial effects through a novel mechanism of action and we may not want to compromise this potential clinical impact by developing compounds with broad-spectrum activity and a common mechanism of action in other therapeutic areas.…”

Two New Antiprotozoal Diterpenes From the Roots of Acacia nilotica

“…This assay is cheap and allows for efficient and reproducible screening of compounds for activity against cultured cells and is therefore commonly employed in parasitology (Räz et al, 1997;Gould et al, 2008). In addition, the compound and mixtures were investigated for toxicity in HEK cells and for cross-resistance to the commonly used melaminophenyl arsenical and diamidine classes of trypanocides (Bridges et al, 2007;Giordani et al, 2019). PAN-76, a mixture of compounds 1 (80%) and 3 (20%), showed promising antitrypanosomal activity with lowest EC 50 of 4.27 ± 0.06 μg/ml against T. evansi (Table 2).…”

Minor Groove Binders MGBs: A Mini Review

“…Many methods were adopted for the modification of Distamycin A and Netropsin [32]. Among them are: changes can be made to the head group, tail group or the heterocyclic rings.…”

“…In recent years, a renewed interest in variety of animal trypanocides has appeared because of the disease's effect on the availability of food, and the arrangement of a product development partnership, and the Global Alliance for Livestock Veterinary. [32] Diminazene isometamidium chloride ethidium bromide…”