Diospyrin: biosynthesis, distribution in the plant kingdom, and therapeutic potential

Abstract Diospyrin, a naturally occurring bisnaphthoquinone, is chemically known as 5-hydroxy-6-(5-hydroxy-7-methyl-1,4-dioxonaphthalen-2-yl)-7-methylnaphthalene-1,4-dione. It was first isolated from the heartwood of Diospyros montana Roxb. (Ebenaceae) and later was found in several species of the genera Diospyros and Euclea . This bisnaphthoquinone is biosynthesized through the dimerization of 7-methyljuglone, a 1,4-naphthoquinone, via C-2 and C-6’ coupling. Previous in vitro , in vivo and in silico studies have established diospyrin as a bioactive compound with therapeutic potentials; the most prominent therapeutically relevant bioactivities include its antibacterial (especially against Mycobacterium and Staphylococcus species), anticancer/antitumour (mainly against Ehrlich ascites carcinoma, blood, breast, cervical, colon, lung, prostate and skin cancer cell lines), and antiparasitic (particularly against Leishmania , Plasmodium and Trypanosoma parasites) properties. In addition to three major activities, diospyrin was found to possess antiallergic, antidiabetic, antifungal, anti-inflammatory, antinociceptive, antioxidant, antiviral, neuroprotective, and sedative properties. Some information on the plausible mechanisms of action of diospyrin for its major bioactivities is also available in the literature. Diospyrin was shown to produce a certain level of cytotoxicity in normal cells, hepatotoxicity and mutagenicity. Overall, diospyrin could be considered a structural lead for developing new therapeutics for cancers and bacterial and parasitic infections, albeit further preclinical and clinical studies with diospyrin and its structural analogues are still needed. This review presents a comprehensive and updated overview, and a critical appraisal of published information until February 2025 on diospyrin ( 1 ), including its occurrence in the plant kingdom, biosynthesis, therapeutic potential, mechanisms of action and toxicity.