Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

• Midori A. Arai,
• Kyoko Uchida,
• Samir K. Sadhu,
• Firoj Ahmed and
• Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

• products with a complex structure. Physalins (1–7) were isolated from Solanum nigrum (Solanaceae) collected in Bangladesh by using our cell-based assay. The isolated physalins included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 showed strong inhibition of GLI1 transcriptional activity

• inhibitory activity. Interestingly, physalin H (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor physalin G (2) did not show inhibition of GLI1-DNA complex formation. Keywords: Hedgehog inhibitor; Hedgehog signal; natural products; physalins; Solanum nigrum; Introduction

• ) inhibited GLI1 binding to its DNA binding domain as assessed by our previously reported electrophoresis mobility shift assay (EMSA). Results and Discussion Isolation of physalins Among our extract library, Solanum nigrum was identified as an active plant with our cell-based assay screening. After the