Diaporthe species produce versatile secondary metabolites (SMs), including terpenoids, fatty acids, polyketides, steroids, and alkaloids. These structurally diverse SMs exhibit a wide range of biological activities, including cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, and phytotoxic activities, which could be exploited in the medical, agricultural, and other modern industries. This review comprehensively covers the production and biological potencies of isolated natural products from the genus Diaporthe associated with terrestrial and marine origins. A total of 275 SMs have been summarized from terrestrial (153; 55%) and marine (110; 41%) origins during the last twelve years, and 12 (4%) compounds are common to both environments. All secondary metabolites are categorized predominantly on the basis of their bioactivities (cytotoxic, antibacterial, antifungal, and miscellaneous activity). Overall, 134 bioactive compounds were isolated from terrestrial (92; 55%) and marine (42; 34%) origins, but about half the compounds did not report any kind of activity. The antiSMASH results suggested that Diaporthe strains are capable of encoding a wide range of SMs and have tremendous biosynthetic potential for new SMs. This study will be useful for future research on drug discovery from terrestrial and marine natural products.

Two new xanthone derivatives, pestalotiones A (1) and B (2), one new diphenyl ketone riboside, pestalotione C (7), and one new diphenyl ether, pestalotione D (8), along with five known compounds isosulochrin dehydrate (3), 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), isosulochrin (5), chloroisosulochrin (6), and pestalotether D (9), were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). The structures of the new compounds were unambiguously deduced by HRESIMS and 1D/2D-NMR spectroscopic data. Compound 6 showed modest cytotoxicity against the HeLa cell line with an IC₅₀ value of 35.2 μM. Compound 9 also showed cytotoxic to the HeLa and MCF-7 cell lines, with IC₅₀ values of 60.8 and 22.6 μM, respectively. Additionally, compounds 1 and 2 exhibited antioxidant activity in scavenging DPPH radical with IC₅₀ values of 54.2 and 59.2 μg/mL, respectively.

One new pyridinone alkaloid pseudogymnone A (1) and one new tricyclic polyketide penijanthinone C (2), together with six known compounds, harzianic acid (3), 3-methyl-2-(2-nonenyl)-4(1H)-quinolinone (4), emodic acid (5), alaternin (6), violaceol-I (7), and violaceol-II (8), were obtained from the Cordyceps-colonizing fungus Pseudogymnoascus roseus. The structures and absolute configurations of the isolated compounds were elucidated through a combination of NMR and MS spectroscopic analyses, ECD calculations, and X-ray crystallography. Compound 3 exhibited obvious cytotoxicity against A549 (IC₅₀ = 4.2 µM) and MGC (IC₅₀ = 3.8 µM) cell lines. Integrated network pharmacology and molecular docking analyses indicated that compound 3 exerts potential anti-gastric-cancer effects by modulating multiple cancer-related signaling pathways, with EGFR identified as a potential target of compound 3.