Natural antifungal agents are generally broad-spectrum compounds with low mammalian and environmental toxicity. Cladosporin is a naturally occurring fungal metabolite mainly isolated from the endophytic fungus Cladosporium cladosporioides. This review article summarizes the chemistry and biological properties of cladosporin covering references published from 1971–2016, including the source, phytochemical characterization, biosynthesis, total synthesis, structure and activity (SAR), and biological activity of cladosporin. Cladosporin exhibited potent antibacterial, antifungal, insecticidal, and anti-inflammatory activities, as well as plant growth regulatory effects. More importantly, cladosporin was identified as having potent, nanomolar, antiparasitic activity against both Plasmodium falciparum blood and liver stages via specific inhibition of protein synthesis. This provides a new approach for the design of isocoumarin-based compounds for the treatment of malaria. Herbicidal activity and antifungal activity against Cryptococcus neoformans (IC50 value of 17.7 μg/mL) of cladosporin are also described here in the review for the first time. Cladosporin selectively inhibited the growth of a monocot (agostis) and showed no activity against a dicot (lettuce), which indicates its great potential as a selective herbicide for monocots in agriculture use. The above data suggest that cladosporin has great potential utility as a lead compound in the development of agrochemicals against certain plant pathogens and pharmaceuticals against drug-resistant bacteria and parasites.
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