New austalide derivative from the marine-derived Aspergillus sp. and evaluation of its biological activity (preprint)

ABSTRACT

Chemical investigation of the ethyl acetate extract of Aspergillus sp. isolated from the soft coral Sinularia species resulted in the isolation of one new meroterpenoid austalide X ( 1 ), one known austalide W ( 2 ), six known prenylated indole diketopiperazine alkaloids ( 3-8 ) and phthalic acid and its ethyl derivative ( 9-10 ) . The structures were established using 1D and 2D NMR experiments supported by UV analysis and ESI-MS (Electrospray ionization mass spectrometry). The effect of changing the fermentation media was also investigated using LC-PDA-MS (Liquid chromatography-photodiode-array-mass spectrometry) employing rice and beans media. It showed significant quantitative and qualitative variations particularly in the diketopiperazine content. In vitro cytotoxic evaluation was performed using MTT assay. Results showed that the examined compounds revealed weak to moderate activities where the new meroterpenoid, austalide X ( 1 ) displayed IC 50 value of 51.6 µg/mL. In silico molecular docking was done to evaluate COVID-19 inhibitory potential of isolated compounds on 2019-nCoV main protease, spike glycoprotein and Angiotensin-Converting Enzyme 2 (ACE2). Compound (10) followed by compound (9) exerted a potent inhibition on all the examined proteins with high fitting scores. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) predication performed in silico showed that most of the isolated compounds revealed reasonable pharmacokinetic, pharmacodynamic and toxicity properties.