Integracin B

Integracins A (1) and B (2), potent HIV-1 integrase inhibitors, and 15'-dehydroxy-integracin B (3) were isolated for the first time from Chinese mangrove plant Sonneratia hainanensis. Their absolute configurations were determined by the Mosher's method and specific rotation analysis of alcohols (6 and 7) obtained from integracin A in two steps and by chemical correlation. Integracin A (1) also exhibited significant cytotoxicity against the tumor cell lines HepG2 and NCI-H460 with both 100% inhibitions at 25 µg/ml.

Two new polyketides, cytospyrone (1), cytospomarin (2), together with three known metabolites dimethoxyphtalide (3), integracin A (4) and integracin B (5), were isolated from the culture of Cytospora sp. from the Chinese mangrove Ceriops tagal. Their structures were elucidated by extensive spectroscopic analyses and time dependent density functional theory (TDDFT), calculation of electronic circular dichroism (ECD) and optical rotation (OR) data. Compound 2 displayed weak inhibitory activity against Escherichia coli GIM1.201 (minimum inhibitory concentration (MIC) value of 0.35 mM). Compounds 4 and 5 displayed significant cytotoxicity against human cancer cell line HepG2 (IC50 values of 5.98 ± 0.12 µM and 9.97 ± 0.06 µM, respectively), more potent than the positive control 5-fluorouracil (IC50 value of 43.50 ± 3.69 µM).

Two new alkylresorcinols named herein 5'-methoxy-integracins A-B (1-2), two new monomeric alkyl aromatic derivatives 3-(7-hydroxyheptyl)-5-methoxyphenol (5) and 7-(3,5-dihydroxyphenyl) heptyl acetate (6), along with four known compounds including integracins A-B (3-4), 2,4-dihydroxy-6-(8-hydroxyoctyl) benzene (7), and cytosporone B (8) were isolated from the endophytic fungus Cytospora rhizophorae A761. The structures of the four new compounds were elucidated by NMR, HRESIMS data, and electronic circular dichroism (ECD) calculations, whereas the compounds 1 and 2 were disclosed as a class of the natural rare-occurring dimeric alkylresorcinol derivatives. Moreover, the bioassays of the new compounds clarified that compound 1 was a potent inhibitor for the α-glucosidase, and compound 2 showed relatively good activity against the tumor cell lines. It is worth mentioning that the known compound integracin B (4) was first reported to display significant antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 6.25 μg ml-1.