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The Acanthamoeba macromolecular synthesis machinery refers to the integrated systems of DNA replication, RNA transcription, and protein translation within Acanthamoeba species, which are free-living amoebae capable of causing sight-threatening keratitis and fatal granulomatous amoebic encephalitis (Khan, 2006 [1]). This machinery is a critical therapeutic target for aromatic diamidines, such as pentamidine and propamidine, which are believed to enter the amoeba and bind to the minor groove of DNA, subsequently inhibiting the synthesis of essential macromolecules (Siddiqui & Khan, 2012 [2]). By disrupting these fundamental biosynthetic processes, these agents prevent the proliferation of trophozoites and may interfere with the transition to the dormant cyst stage (Lorenzo-Morales et al., 2015 [3]). However, the effectiveness of targeting this machinery is often limited by the presence of the highly resilient cyst stage, which exhibits significantly reduced metabolic activity and lower permeability to drugs (Lloyd, 2014 [4]). Furthermore, many drugs targeting these pathways also exhibit toxicity toward host cells, such as the corneal epithelium, necessitating careful clinical management (Siddiqui et al., 2016 [5]).
Inhibition of DNA, RNA, and protein synthesis through DNA binding or interference with biosynthetic enzymes.
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