Five undescribed butenolides including two pairs of enantiomers, (+)-asperteretal G (1a), (−)-asperteretal G (1b), (+)-asperteretal H (2a), (−)-asperteretal H (2b), asperteretal I (3), and para-hydroxybenzaldehyde derivative, (S)-3-(2,3-dihydroxy-3-methylbutyl)-4-hydroxybenzaldehyde (14), were isolated together with ten previously reported butenolides 4–13, from the coral-derived fungus Aspergillus terreus SCSIO41404. Enantiomers 1a/1b and 2a/2b were successfully purified by high performance liquid chromatography (HPLC) using a chiral column, and the enantiomers 1a and 1b were new natural products. Structures of the unreported compounds, including the absolute configurations, were elucidated by NMR and MS data, optical rotation, experimental and calculated electronic circular dichroism, induced circular dichroism, and X-ray crystal data. The isolated butenolides were evaluated for antibacterial, cytotoxic, and enzyme inhibitory activities. Compounds 7 and 12 displayed weak antibacterial activity, against Enterococcus faecalis (IC₅₀ = 25 μg/mL) and Klebsiella pneumoniae (IC₅₀ = 50 μg/mL), respectively, whereas 6 showed weak inhibitory effect on acetylcholinesterase. Nevertheless, most of the butenolides showed inhibition against pancreatic lipase (PL) with an inhibition rate of 21.2–73.0% at a concentration of 50 μg/mL.

Ten secondary metabolites were isolated from cultures of the marine coral-derived fungus Aspergillus terreus SCSIO41404. The compounds were identified as monacolin K (1), methyl ester of lactone ring-opened monacolin K (2), asperterreusine C (3), 4-hydroxybenzaldehyde (4), 4-hydroxy-3-(3-methylbut-2-en-1-yl) benzaldehyde (5), kojic acid (6), p-hydroxyphenylacetic acid methyl ester (7), o-hydroxyphenylacetic acid methyl ester (8), N-(2-hydroxyphenyl)-acetamide (9), and (S)-methyl 2-acetamido-3-phenylpropanoate (10), by comparing the spectroscopic data with the reported literature values. They were evaluated for their cytotoxic, antibacterial, and enzyme (pancreatic lipase and acetylcholinesterase) inhibitory activities. Monacolin K (1) and its derivative (2) were revealed with obvious pancreatic lipase (PL) inhibitory effects. The in silico molecular docking with PL protein was further performed to understand the binding effects, and it is suggested that the ring opening of the monacolin K facilitates for the PL inhibitory activities.

Nine new mycophenolic acid derivatives, penicacids O–W (1–9), two first-time reported natural products (10, 11), and five known compounds (12–16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a South China Sea sediment sample. Their structures were determined using NMR, HRESIMS, and optical rotatory dispersion (ORD) spectra, electronic circular dichroism (ECD) calculations, X-ray crystallography, and modified Mosher’s methods. Eight of these compounds were evaluated for anti-proliferative effects against nine human cancer cell lines and the IC₅₀ values ranged from nM to μM levels. Compounds 5, 7–9 showed potent inhibition activity against MOLM-13 acute myeloid leukemia cells with IC₅₀ values between 0.13 and 1.13 μM.

Two new prenylated xanthones, emerixanthones F (1) and G (2), were isolated from the soft coral-derived fungus Aspergillus stellatus SCSIO41406, along with eight known compounds (3 - 10). Their structures were elucidated through the analysis of NMR spectroscopy, MS data, experimental and calculated NMR and ECD values. Nine compounds (2-10) were tested for their antibacterial effects against three human pathogenic bacteria, and compound 4 demonstrated moderate antibacterial activity against Micrococcus luteus ML01 with an MIC value of 8.9 μg/mL.

Natural products continue to serve as a foundational source of pharmacologically relevant molecules due to their chemical diversity and evolutionary optimization for biological interaction. This systematic review and meta-analysis synthesize current evidence on selected classes of bioactive natural products, including L-ascorbic acid and its derivatives, Annonaceous acetogenins, methylxanthines, butenolides, and marine-derived sesterterpenes, with a focus on their mechanistic actions and therapeutic potential. Emphasis is placed on compounds that modulate oxidative stress, mitochondrial bioenergetics, epigenetic regulation, and pathogen-specific metabolic pathways. Pharmacological concentrations of L-ascorbic acid demonstrate prooxidant activity that selectively induces cytotoxicity in cancer cells while also functioning as a cofactor for epigenetic enzymes involved in DNA demethylation. Annonaceous acetogenins, particularly chatenaytrienins, show potent inhibition of mitochondrial complex I, leading to reactive oxygen species generation and programmed cell death, although concerns regarding neurotoxicity remain. Marine suvanine sesterterpenes selectively inhibit isocitrate lyase in the glyoxylate cycle, a pathway essential for fungal virulence but absent in humans, highlighting a promising antivirulence strategy. Butenolide derivatives exhibit a wide spectrum of activities ranging from cytoprotection and cytoproliferation to antifungal and antibacterial effects, with structure–activity relationships guiding potency optimization. Quantitative synthesis of cytotoxicity and antifungal efficacy data supports the therapeutic relevance of these compounds while underscoring the importance of mechanistic specificity. Collectively, this review integrates biochemical, cellular, and computational evidence to evaluate the translational potential and limitations of these natural products in drug discovery.