Pyranodipyran Derivatives with Tyrosyl DNA Phosphodiesterase 1 Inhibitory Activities and Fluorescent Properties from Aspergillus sp. EGF 15-0-3.

Four new benzodipyran racemates, namely (±)-aspergiletals A-D ( 3 - 6 ), representing a rare pyrano[4,3- h ]chromene scaffold were isolated together with eurotiumide G ( 1 ) and eurotiumide F ( 2 ) from the soft-coral-derived fungus Aspergillus sp. EGF 15-0-3. All the corresponding optically pure enantiomers were successfully separated by a chiral HPLC column. The structures and configurations of all the compounds were elucidated based on the combination of NMR and HRESIMS data, chiral separation, single-crystal X-ray diffraction, quantum chemical 13 C NMR, and electronic circular dichroism calculations. Meanwhile, the structure of eurotiumide G was also revised. The TDP1 inhibitor activities and photophysical properties of the obtained compounds were evaluated. In the TDP1 inhibition assay, as a result of synergy between (+)- 6 and (-)- 6 , (±)- 6 displayed strong inhibitory activity to TDP1 with IC 50 values of 6.50 ± 0.73 μM. All compounds had a large Stokes shift and could be utilized for elucidating the mode of bioactivities by fluorescence imaging.