Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IP_3-4K.

ABSTRACT: New antifungals are urgently needed to treat deadly fungal infections. Targeting the fungal inositol polyphosphate kinases IP_3-4K (Arg1) and IP₆K (Kcs1) is a promising strategy as it has been validated genetically to be crucial for fungal virulence but never pharmacologically. We now report the synthesis of DT-23, an analogue of N2-(m-trifluorobenzylamino)-N6-(p-nitrobenzylamino)purine (TNP), and demonstrate that it more potently inhibits recombinant Arg1 from the priority pathogen Cryptococcus neoformans (Cn) (IC₅₀ = 0.6 μM) than previous analogues (IC₅₀ = 10-30 μM). DT-23 also inhibits recombinant Kcs1 with similar potency (IC₅₀ = 0.68 μM) and Arg1 and Kcs1 activity in

SUBMITTER: Desmarini D 

PROVIDER: S-EPMC11997995 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature