Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens

Bioorg Med Chem. 2015 Aug 1;23(15):4150-4154. doi: 10.1016/j.bmc.2015.06.058.

Midori A Arai ¹, Kyoko Uchida ², Samir K Sadhu ³, Firoj Ahmed ⁴, Takashi Koyano ⁵, Thaworn Kowithayakorn ⁶, Masami Ishibashi ⁷

Affiliations

1 Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: midori_arai@chiba-u.jp.
2 Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
3 Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh.
4 Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.
5 Temko Corporation, 4-27-4 Honcho, Nakano, Tokyo 164-0012, Japan.
6 Faculty of Agriculture, Khon Kaen University, Khon Kaen 40002, Thailand.
7 Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: mish@chiba-u.jp.

PMID: 26178912 DOI: 10.1016/j.bmc.2015.06.058

Abstract

The Hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a Cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50=7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.

Keywords

Artocarpus communis; Hedgehog signal; Hyptis suaveolens; Inhibitor; Natural products.

Name
Email *

	Sorry, but the email address you supplied was invalid.