As one of the common malignancies that threaten human life, bladder cancer occurs frequently with a high mortality rate in the world, due to its invasion, recurrence and drug resistance. Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities, especially in the area of cancer. Brefeldin A (BFA) is a natural Arf-GEFs inhibitor, but due to the low aqueous solubility, strong toxicity, and poor bioavailability, it is urgent to conduct structural optimization research. Herein, a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines. It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82 (IC₅₀ = 0.079 and 0.081 μmol/L) with high selectivity index (SI = 14.68 and 14.32), suggesting a superior safety to BFA. In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model (TGI = 52.63%) and prolonged the survival time (ILS = 68.16%) in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells. Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells. Overall, CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms.

To enhance the biological activity of the natural product geodin (1), isolated from the marine-derived fungus Aspergillus sp., a series of new ether derivatives (2–37) was designed and semisynthesized using a high-yielding one-step reaction. In addition, the insecticidal and antibacterial activities of all geodin congeners were evaluated systematically. Most of these derivatives showed better insecticidal activities against Helicoverpa armigera Hübner than 1. In particular, 15 showed potent insecticidal activity with an IC₅₀ value of 89 μM, comparable to the positive control azadirachtin (IC₅₀ = 70 μM). Additionally, 5, 12, 13, 16, 30 and 33 showed strong antibacterial activity against Staphylococcus aureus and Aeromonas salmonicida with MIC values in the range of 1.15–4.93 μM. The preliminary structure–activity relationships indicated that the introduction of halogenated benzyl especially fluorobenzyl, into 1 and substitution of 4-OH could be key factors in increasing the insecticidal and antibacterial activities of geodin.

A series of 6 novel ester derivatives 2-7 of natural product geodin 1 were designed and semi-synthesized through one mild step reaction with high yield. Compounds 2-7 showed strong inhibitory activities against Staphylococcus aureus in the range of 2.35-9.41 mu M. Compounds 4 and 7 showed very strong inhibitory activities against antifouling bacteria Aeromonas salmonicida with MICs of 2.42 mu M and 4.56 mu M respectively. Most notably compounds 3-7 showed potent antifungal activities against Candida albicans in the range of 0.59-2.44 mu M. Particularly, compound 3 showed the highest antifungal activity against C. albicans with a MIC value of 0.59 mu M. The preliminary structure activity relationship of these derivatives showed that replacement of 4-OH group with benzoyl substituents could enhance the antibacterial and antifungal activities of geodin 1.

Objectives: Microorganisms produce optically single bioactive natural products; the process is cheap as compared to chemical synthesis and environmentally friendly. Geodin 1 was isolated from the soft coral-derived fungus Aspergillus sp. It has a broad range of biological activities such as antiviral, antimicrobial, glucose stimulator for rat adipocytes, enhancement of fibrinolytic and cytotoxic activities, and is a subunit of the first nonpeptide and inhibitory active galanin receptor. In this work, we studied the effects of sodium chloride (NaCl) salt concentration on the production of geodin 1 and improved its yield to a multi-gram quantity through media optimization from a marine-derived fungus Aspergillus sp. Methods: The fungal strain was cultivated at various concentrations of NaCl salt in rice medium and extracted after different intervals of time. Results: The yield of geodin 1 was 137.2 mg/L at optimal conditions. The optimal conditions for the high yield of geodin 1 were found as rice medium with 2.0% NaCl salt and 3 weeks incubation at room temperature. Conclusions: The concentration of NaCl salt greatly affects the yield of geodin and hence its biosynthetic pathway.

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls—a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core—has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative—CHNQD-00824—derived from the marine compound library as a potential anticancer agent. The cytotoxic activities of the CHNQD-00824 compound were evaluated against 13 different cell lines with IC₅₀ values from 0.16 to 7.64 μM. Further study showed that CHNQD-00824 inhibited the proliferation and migration of cancer cells, possibly by inducing DNA damage. Acridine orange staining demonstrated that CHNQD-00824 promoted apoptosis in zebrafish embryos. Notably, the anti-cancer effectiveness was verified in a doxycin hydrochloride (DOX)-induced liver-specific enlargement model in zebrafish. With Solafinib as a positive control, CHNQD-00824 markedly suppressed tumor growth at concentrations of 2.5 and 5 μM, further highlighting its potential as an effective anticancer agent.

Marine-derived microorganisms are vital sources of bioactive secondary metabolites. Secondary metabolites of coral-derived fungi have several essential bioactivities. Asterric acid 1 is a broad-spectrum bioactive secondary metabolite of several fungal genera, especially Aspergillus and Penicillium. It has a wide range of interesting bioactivities such as antifungal, antimicrobial, cytotoxic, fungicidal, pesticidal, nematicidal, seed germination inhibition, anti-HIV activity, as a first non-peptide for endothelin binding inhibition, anti-plasmodial activity against the erythrocyte stages of chloroquine-resistant Plasmodium falciparum, having vascular endothelial growth factor inhibitory activity and as medicine for the initial stage of an endothelin receptor agonist. In this study, the yield of asterric acid was improved to a multi-gram quantity from the soft coral-derived fungus Aspergillus sp. through media optimization. The pure spoors of Aspergillus sp. were fermented at room temperature in the absence of sodium chloride salt. The yield of asterric acid was 650 mg/L at optimal conditions. The optimal conditions for the high yield of asterric acid were found as rice medium, room temperature, 56 days incubation and absence of sodium chloride salt.