Cytotoxic homoisoflavonoids from the bulbs of Bellevalia flexuosa

Four new homoisoflavonoids, 7-O-methyl-8-demethoxy-3′-hydroxy-3,9-dihydropunctatin (4), 6-hydroxy-8-demethoxy-4′-O-methyl-3,9-dihydropunctatin (8), 7,4′-O-dimethyl-8-demethoxy-3,3′-dihydroxy-3,9-dihydropunctatin (13), and 7-O-methyl-3-hyroxy-3,9-dihydropunctatin (14) were identified from a chloroform extract of the bulbs of Bellevalia flexuosa, along with 13 known analogues. The structures were determined by analysis of HRMS and NMR data, while ECD spectroscopy enabled the assignment of the absolute configurations of the new compounds 4, 8, 13 and 16. The cytotoxic activities of the isolated compounds (1–17) were evaluated using a panel of human cancer cell lines. Compounds 2 and 7 were the most potent against the MDA-MB-435 (melanoma) cancer cell line with IC50 values of 1.6 and 2.0 μM, respectively, and were essentially equipotent against the OVCAR3 (ovarian) cancer cell line with IC50 values of 9.5 and 10.8 μM, respectively. However, compound 7, with an IC50 value of 3.6 μM, was the most potent against the MDA-MB-231 (breast) cancer cell line.This research was supported, in part, by the Deanship of Research, Jordan University of Science and Technology , Irbid, Jordan (Grant No. 284/2017 ) and via program project grant P01 CA125066 from the National Cancer Institute / National Institutes of Health , Bethesda, MD, USA. Appendix AScopu

The value of open-source clinical science in pandemic response: lessons from ISARIC

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