Research on Secondary Metabolites and Biological Activities of Trichoderma lucidum CIB-604
Chaetomium, a genus of fungi belonging to the Ascomycetes order, Sphaerales family, and Chaetomiaceae family, is widely present in air, soil, and biological organisms. Currently, over 400 species have been reported. Previous studies have shown that fungi belonging to the genus Trichoderma can produce secondary metabolites with diverse structural types, among which cell relaxants and azaphilone compounds are the main types. At the same time, secondary metabolites of Trichoderma fungi have a wide range of biological activities, such as antibacterial, anti-inflammatory, cytotoxic, etc. Our research group has long been committed to the discovery of secondary metabolites and their biological activities in fungi of the genus Trichoderma. We have isolated various types of active substances with different structural types from secondary metabolites of Trichoderma, such as C. cochlides, C. convolutum, C. globorum CIB-160, and C. gracile. C. funicola is a potential pathogen that has been found in infected skin tissue. In 1969, a macrocyclic lactone compound was reported isolated from Trichoderma lucidum. In 1987, Itoh et al. isolated it from C Funicola JS 525 isolated ubiquinone compounds. At present, there are only two research reports on the secondary metabolites of rope hair shell, and there is a lack of relevant biological activity research reports. This article systematically studied the secondary metabolites of a strain of Trichoderma funicola CIB-604, and tested the antibacterial and cytotoxic activities of some compounds. Here, we will report on the structure and biological activity of the secondary metabolites produced by this bacterium.

In this study, eight secondary metabolites were isolated from the solid-state fermentation of rice by a strain of Aspergillus niger (C. funicola CIB-604), including three isoquinoline alkaloids (1-3) and five sterol compounds (4-8), all of which were isolated from Aspergillus niger for the first time. Compounds 1-3 were the first structurally novel quinoline alkaloids discovered by our research group from the secondary metabolites of C. indica 3.202 in India. So far, Aspergillus niger is the second fungus capable of producing such novel quinoline alkaloids, suggesting that it may contain the same quinoline alkaloid biosynthesis pathway as C. indica. This paper conducted antibacterial and cytotoxic activity tests on compounds 1-6. The antibacterial activity results showed that at a concentration of 100 μ g/mL, compounds 1-6 did not exhibit inhibitory effects on Escherichia coli, Bacillus subtilis, and Candida albicans; The cytotoxic activity results showed that compounds 2 and 4 exhibited cytotoxic activity against human tumor cells SK-Hep-1, A549, HCT-116, and MCF-7, and compound 4 had a stronger inhibitory effect on tumor cells than compound 2; The results of flow cytometry analysis showed that compounds 2 and 4 mainly induced early apoptosis in SK-Hep-1 cells, while compound 2 had little effect on early and late apoptosis in A549 cells, while compound 4 mainly induced late apoptosis in A549 cells. This article reports for the first time the cytotoxic activity of compound 2 on tumor cells. The analysis results show that compound 3 is a diastereomer of 2, but its cytotoxic activity is significantly lower than compound 2, indicating that the relative configuration between hydroxyl and isopropyl groups has a significant impact on its cytotoxic activity. Compared with compounds 5 and 6, compound 4 exhibits significant cytotoxic activity. Analysis of its structural features reveals a typical active center – α, β – unsaturated carbonyl structural unit – in the molecular structure of compound 4, which can undergo alkylation reaction with the thiol groups of proteins in cells, thereby binding to tumor cells and killing them. In summary, the research results on the secondary metabolites and biological activities of Trichoderma lucidum CIB-604 in this paper have laid a scientific foundation for the scientific understanding and rational development and utilization of this bacterium.