Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2–18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.


NO.
Contents Page

Figure S1
The UV spectrum of 1 in MeOH S4

Figure S2
The ECD spectrum of 1 in MeOH S4

Figure S3
The HR-ESI-MS data of 1 S5

Figure S9
The HR-ESI-MS data of 2 S8

Figure S12
The HR-ESI-MS data of 3 S9

Figure S15
The HR-ESI-MS data of 4 S11

Figure S18
The HR-ESI-MS data of 5 S12

Figure S21
The HR-ESI-MS data of 6 S14

Figure S24
The HR-ESI-MS data of 7 S15

Figure S27
The HR-ESI-MS data of 8 S17

Figure S30
The HR-ESI-MS data of 9 S18

Figure S33
The HR-ESI-MS data of 10 S20

Figure S36
The HR-ESI-MS data of 11 S21

Figure S39
The HR-ESI-MS data of 12 S23

Figure S40
The ECD spectrum of 12 in MeOH S23

Figure S43
The HR-ESI-MS data of 13 S25

Figure S46
The HR-ESI-MS data of 14 S26

Figure S49
The HR-ESI-MS data of 15 S28

Figure S52
The HR-ESI-MS data of 16 S29

Figure S55
The HR-ESI-MS data of 17 S31

Figure S58
The HR-ESI-MS data of 18 S32

Figure S60
The