Yiwen Tao

Introduction: HPLC analysis indicated that the mangrove endophytic fungus Aspergillus fumigatus BF-18 exhibited an abundant profile of secondary metabolites. To isolate and identify secondary metabolites from the culture extract of the fungus Aspergillus fumigatus BF-18, and evaluate the cytotoxic activity of these isolates. Methods: The strain Aspergillus fumigatus BF-18 was fermented statically using rice solid medium and extracted with MeOH. The extract was purified by silica gel and Sephadex LH-20 gel column chromatography, followed by semi-preparative HPLC. The structures of the isolated compounds were identified by analyses of ESI-MS and NMR spectroscopic data. The cytotoxic activities of the isolates were assayed using the MTT method. Results: Nine alkaloid compounds (1-9) were identified, including a new indole-quinoline alkaloid named chaetominine B (1). In MTT bioassays, pseurotin G (8) significantly inhibited the proliferation of non-small-cell lung cancer cell lines H1299 with an IC50 value of 1.1 μM. Discussion: Previous reports revealed that chaetominine (2) inhibited human leukemia K562 and colon cancer SW1116 cell growth at the nanomolar level. However, in this work, chaetominine (2) only exhibited weak anti-proliferative activity against H1299 and A549 cells, indicating that its antitumor activity is highly selective. Conclusion: The endophytic fungus Aspergillus fumigatus BF-18 isolated from mangroves produces cytotoxic alkaloid secondary metabolites with diverse chemical frameworks. The isolation and identification of the new compound 1 enriches the chemical diversity of indole-quinazoline alkaloids.

Eleven compounds were isolated from the secondary metabolites of the marine fungus Aureobasidium pullulans 8438, including three novel compounds, 9-hydroxy-massoia lactone (1), Ethyl p-hydroxybenzoate (3 R,5R)-3,5-dihydroxydecanoate (2), and (R)-9,10-dihydroxypropyl 4-hydroxy-5-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien -1-yl) benzoate (3), along with 8 known compounds (4-11). Compounds 1, 2 and 4-9 are decanoic acid derivatives, while both compounds 3 and 11 are 3-farnesyl-p-hydroxybenzoic acid derivatives. The planar structures of the new compounds were determined using high-resolution mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) data. Their absolute configurations were established through the Snatzke method, quantum chemical calculations (including computational NMR and ECD), and DP4+ analysis. All isolated compounds were evaluated for their cytotoxic effects against human non-small cell lung cancer cells A549 and human cervical cancer cells HeLa.

Investigation of secondary metabolites from the mangrove endophytic fungus Talaromyces sp. SAF14 led to the isolation of two new polyketides, methyl (R)-3-(6,8-dihydroxy-7-methoxy-1-oxoisochroman-3-yl)propanoate (1), (R)-3-(5,8- dihydroxy-1-oxoisochroman-3-yl)propanoic acid (2), together with four known alkaloids (3-6). The planar structures of new compounds were elucidated by comprehensive analysis of HR-ESI-MS and NMR data. The absolute configurations were determined by comparison of the calculated ECD spectrum with the measured one. All the isolated compounds were tested for cytotoxic activities against three human cancer cell lines. The known beauvericin (3) exhibited strong cytotoxic activity against A549, MCF-7, and KB cell lines with IC₅₀ values of 5.36 ± 2.49, 1.96 ± 1.09 and 4.46 ± 0.68 μM, respectively.

Background: Gambogic acid (GA) is a natural product from the resin of the Garcinia species, which showed significant activity in the induction of apoptosis. It can be one promising lead compound for the design and synthesis of new anticancer drugs. Objective: The objective of the current study is to design novel nitrogen-contained GA derivatives with better anti-cancer activities and study the effect of the introduction of different nitrogen-contained groups on the activity of GA. Methods: The designed 15 derivatives were synthesized via esterification or amidation of 30-carboxylate. The synthetic compounds were characterized via different spectroscopic techniques, including X-ray single crystal diffraction, MS and NMR. The cytotoxic activity of the designed derivatives was evaluated in vitro against A549, HepG-2, and MCF-7 cell lines using methyl thiazolyl tetrazolium (MTT) test. Results: 15 nitrogen-contained GA derivatives were successfully synthesized and established. Based on the IC50 values, compounds 9, 10, 11 and 13 showed stronger inhibitory effects on A549, HepG-2, MCF-7 cell lines than GA, while 9 is the most active compound with IC50 value of 0.64-1.49 μM. Most derivatives of GA with esterification of C-30 including cyano-benzene ring were generally weaker than those of pyrimidinyl-substituted derivatives. In addition, length of alkyl linkers between C-30 of GA and nitrogen-contained group produced different effects on A549, HepG-2 and MCF-7 cell lines. Conclusion: The structure-activity relationship results show that aromatic substituent and linker length play important roles to improve the anticancer activities, while compound 9 with pyrimidine substituent and C-C-C linkers is the most active derivative against tested cell lines, and is a promising anti-cancer agent for further development.