New polyketides and cytotoxic alkaloids from the mangrove endophytic fungus Talaromyces sp. SAF14.

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.

Design, Synthesis and Anti-cancer Evaluation of Nitrogen-containing Derivatives of 30-Carboxyl of Gambogic Acid.

BACKGROUND: Gambogic acid (GA) is a natural product from the resin of the Garcinia species, which showed significant activity in the induction of apoptosis. .t 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.

Two new alkaloids from the endophytic fungus Aspergillus fumigatus SAS10 isolated from the mangrove tree Sonneratia apetala.

Two new alkaloids designated aspernigrin E (1) and pyranonigrin L (2) were isolated from mangrove endophytic fungus Aspergillus fumigatus SAS10, together with the known alkaloid compounds pyranonigrin A (3), asperazine (4), (+)-iso-pestalazine A (5), pestalazine A (6), and pestalazine B (7). The planar structures of the new compounds were elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configurations of compounds 1 and 2 were determined by comparison of the electronic circular dichroic (ECD) spectra with the calculated ECD spectra. All these compounds were tested for anti-bacterial activity.

Cytotoxic tetronic acid derivatives from the mangrove endophytic fungus Hypomontagnella monticulosa YX702.

Three new tetronic acid derivatives, nodulisporacid A ethyl ester (3), isosporothric acid methyl ester (4), and (R)-3-(methoxycarbonyl)-2-methyleneundecanoic acid (5) were isolated from mangrove endophytic fungus Hypomontagnella monticulosa YX702, together with three known analogues nodulisporacid A (1), nodulisporacid A methyl ester (2), and dihydrosporothriolide (6). The structures of these new compounds were elucidated by analysis of NMR and HR-ESI-MS spectroscopic data. In addition, the absolute configuration of nodulisporacid A (1) was confirmed by single-crystal X-ray diffraction for the first time. Subsequently, the absolute configuration of compounds 2 and 3 were determined by chemical derivatization of nodulisporacid A (1). The absolute configuration of compound 4 and 5 were established by TDDFT ECD calculations. Compounds 1 and 2 exhibited cytotoxic activities against A549 and Hela cancer cell lines with the IC50 values between 5.64 and 8.14 µM.