Drug Discovery and Development on Pma1, Where Are We Now? A Critical Review from 1995 to 2022.

Plasma membrane H⁺ -ATPase (Pma1) is an enzyme uniquely found in plants and fungi. The enzyme controls the nutrient uptake of plants and fungi via an electrochemical gradient processes, which is essential for their survival. Inhibiting Pma1, therefore, constitutes an alternative antifungal target void of toxicity to humans. From a medicinal chemistry point of view, this review provides a first summary of the recent drug design, synthesis, evaluation, and discovery of molecules targeting Pma1 for 25 years from 1995 to 2022.