European Journal of Medicinal Chemistry Reports (Dec 2023)
Discovery and current developments of isoindolinone-based fungal natural products
Abstract
Most fungi generate secondary metabolites essential to their growth or used as chemical defense systems. They produce a large variety of small molecules, notably alkaloids containing an isoindolinone unit in the form of small bicyclic cichorine-type molecules more or less substituted, up to the form of extended, heavily substituted tri- or tetra-cyclic molecules equipped with one or two prenyl side chains. An extended family of more than 170 isoindolinone derivatives produced by mycelial or endophytic fungi has been identified and analyzed. These isoindolinone derivatives include many series such as the andicichorines, aspergillinines, caputmedusins, clitocybins, daldinans, emerimidines, emeriphenolicins, entonalactams, erinaceolactams, erinacerins, fendlerinines, marilines, meyeroguillines, stachartins, stachybotrins, stachybotrysams, sterenins, xylactams, and others compounds endowed with pharmacological properties described here. The family also includes isoindolinone dimers, notably potent fibrinolytic compounds, such as those designated Stachybotrys microspora triprenyl phenol (SMTP) with the lead product SMTP-7 (orniplabin) currently developed for the treatment of stroke. The repertoire of isoindolinone-based natural products produced by fungi is large (in contrast that of vascular plants) and comprises products with marked anti-inflammatory, antiviral, or anticancer activities. All these fungal isoindolinone-based products can be exploited for their medicinal properties and to guide the design of functionalized analogues targeting different enzymes or pathways. The chemical or biosynthetic access to these products is evoked and the most potent derivatives are underlined. Altogether, the review offers an exhaustive repertoire of isoindolinones of fungal origin and their pharmacological properties.
