Microorganisms still remain the main hotspots in the global drug discovery avenue. In particular, fungi are highly prolific producers of vast structurally diverse specialized secondary metabolites, which have displayed a myriad of biomedical potentials. Intriguingly, isocoumarins is one distinctive class of fungal natural products polyketides, which demonstrated numerous remarkable biological and pharmacological activities. This review article provides a comprehensive state-of-the-art over the period 2000–2022 about the discovery, isolation, classifications, and therapeutic potentials of isocoumarins exclusively reported from fungi. Indeed, a comprehensive list of 351 structurally diverse isocoumarins were documented and classified according to their fungal sources [16 order/28 family/55 genera] where they have been originally discovered along with their reported pharmacological activities wherever applicable. Also, recent insights around their proposed and experimentally proven biosynthetic pathways are also briefly discussed.

Lantana camara L. and Lantana montevidensis Briq. (F. Verbenaceae) are invasive ornamental weeds native to the tropical regions of Africa and America. The leaves of both species have been traditionally used as infusions for treating fever, rheumatism, and cancer. LC–MS–MS-guided profiling of the methanolic extracts of the leaves of L. camara and L. montevidensis growing in Egypt led to the putative identification of 59 compounds belonging to terpenoids, flavonoids, iridoid glycosides, phenolic acids, and their derivatives. The in-vitro antioxidants and anti-inflammatory and anticancer activities of the two extracts were investigated. L. camara and L. montevidensis inhibited DPPH^• (IC₅₀ = 34.01 ± 1.32 and 47.43 ± 1.74 µg/mL), ABTS⁺ (IC₅₀ = 30.73 ± 1.42 and 40.37 ± 1.51 µg/mL), and superoxide anion (IC₅₀ = 1.57 ± 0.19 and 1.31 ± 0.14 μg/mL) free radicals. A potent anti-inflammatory effect was observed for both species through the inhibition of elastase release in fMLF/CB-induced human neutrophils (IC₅₀ = 2.40 ± 0.16 and 1.90 ± 0.07 μg/mL). The extracts showed significant cytotoxic activity against a panel of cancer cell lines with the most potent activity against Caco cells (IC₅₀ = 45.65 ± 1.64 and 40.67 ± 1.52 µg/mL for L. camara and L. montevidensis, respectively). Western blotting supported by FACS analysis revealed that the extracts inhibited cancer cell proliferation, reduced metastasis, and induced apoptosis resulting in cell cycle arrest. This was achieved via increasing mRNA and protein expressions of p53 and GSK-3β as well as decreasing the expression of PI3K, Akt, and cyclin D1.

Brown algae comprise up to 2000 species with wide dissemination in temperate zones. A comprehensive untargeted metabolic profiling guided by molecular networking of three uninvestigated Red-Sea-derived brown algae, namely Sirophysalis trinodis, Polycladia myrica, and Turbinaria triquetra, led to the identification of over 115 metabolites categorized as glycerolipids, fatty acids, sterol lipids, sphingolipids, and phospholipids. The three algae exhibited low-to-moderate antioxidant capacity using DPPH and ABTS assays. Preliminary in vitro antiproliferative studies showed that the algal extracts displayed high cytotoxic activity against a panel of cancer cell lines. The most potent activity was recorded against MCF-7 with IC₅₀ values of 51.37 ± 1.19, 63.44 ± 1.13, and 59.70 ± 1.22 µg/mL for S. trinodis, P. myrica, and T. triquetra, respectively. The cytotoxicity of the algae was selective to MCF-7 without showing notable effects on the proliferation of normal human WISH cells. Morphological studies revealed that the algae caused cell shrinkage, increased cellular debris, triggered detachment, cell rounding, and cytoplasmic condensation in MCF-7 cancer cells. Mechanistic investigations using flow cytometry, qPCR, and Western blot showed that the algae induced apoptosis, initiated cell cycle arrest in the sub-G₀/G₁ phase, and inhibited the proliferation of cancer cells via increasing mRNA and protein expression of p53, while reducing the expression of PI3K, Akt, and mTOR.