Bhimamycin A

From the wild-type strain Steptomyces sp. AK 671, three nitrogen-containing octaketides were isolated, bhimamycins F, H and I, besides the known azaanthraquinone utahmycin A and polyketide shunt products SEK 4, SEK 4b, mutactin, dehydromutactin and EM18. The structures were characterized by MS and NMR experiments. The hitherto unknown absolute configuration of the two enantiomers of EM18 was determined by online-CD spectroscopy and quantum-chemical CD calculations. Bhimamycins H and I show weak antibacterial activities, whereas the enzyme phosphodiesterase 4 is strongly inhibited by bhimamycins H and I, which has never been reported for nitrogen-containing octaketides. In addition, bhimamycin H inhibits the enzyme glycogen synthase kinase-3β.

From the ethyl acetate extract of a terrestrial Streptomycete isolate, five new quinone antibiotics, bhimamycin A (2a), B (2b), C (3c), D (5a), E (7) and the new tetralone bhimanone (8) were isolated together with the known microbial products chrysophanol (1a), aloesaponarin II (1b), 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid (1c), adenosine, 2'-deoxyadenosine, phenylacetamide, and 2-(p-hydroxyphenyl)ethanol. The structures of these natural products were deduced from the spectral data and confirmed by comparison with related compounds from the literature and by synthesis.

Chemical investigation on a Streptomyces sp. strain MS180069 isolated from a sediment sample collected from the South China Sea, yielded the new benzo[f]isoindole-dione alkaloid, bhimamycin J (1). The structure was determined by extensive spectroscopic analysis, including HRMS, 1D, 2D NMR, and X-ray diffraction techniques. A molecular docking study revealed 1 as a new molecular motif that binds with human angiotensin converting enzyme2 (ACE2), recently described as the cell surface receptor responsible for uptake of 2019-CoV-2. Using enzyme assays we confirm that 1 inhibits human ACE2 79.7 % at 25 μg/mL.