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

• Published in: Marine drugs Vol. 20; no. 3; p. 211
• Main Authors: Wei, Xia, Wang, Fang-Ting, Si-Tu, Mei-Xia, Fan, Hao, Hu, Jin-Shan, Yang, Hao, Guan, Shan-Yue, An, Lin-Kun, Zhang, Cui-Xian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.03.2022; MDPI
• Subjects: Animals; Anthozoa - microbiology; Aspergillus; Aspergillus - chemistry; Aspergillus - metabolism; Cancer; Carbon; Circular dichroism; Columns (structural); Deoxyribonucleic acid; Dichroism; DNA; Enantiomers; Fluorescence; fluorescent properties; Fungi; High-performance liquid chromatography; HPLC; Hydrocarbons; Liquid chromatography; Models, Molecular; NMR; Nuclear magnetic resonance; Phosphodiesterase; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - isolation & purification; Phosphoric Diester Hydrolases - chemistry; Properties; pyranodipyran derivatives; Pyrans - chemistry; Pyrans - isolation & purification; Pyrans - metabolism; Quantum chemistry; Radiation; Single crystals; soft-coral-derived fungus; tyrosyl DNA phosphodiesterase 1 inhibitory activities; X-ray diffraction; fluorescent properties; tyrosyl DNA phosphodiesterase 1 inhibitory activities; soft-coral-derived fungus; pyranodipyran derivatives
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20030211

Four new benzodipyran racemates, namely (±)-aspergiletals A-D ( - ), representing a rare pyrano[4,3- ]chromene scaffold were isolated together with eurotiumide G ( ) and eurotiumide F ( ) from the soft-coral-derived fungus 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 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 (+)- and (-)- , (±)- displayed strong inhibitory activity to TDP1 with IC 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.