Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens

Midori A. Arai; Kyoko Uchida; Samir K. Sadhu; Firoj Ahmed; Takashi Koyano; Thaworn Kowithayakorn; Masami Ishibashi

doi:10.1016/j.bmc.2015.06.058

Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens

Midori A. Arai, Kyoko Uchida, Samir K. Sadhu, Firoj Ahmed, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

Research output: Contribution to journal › Article

10 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4150-4154
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2015.06.058
Publication status	Published - 2015 Jul 23
Externally published	Yes

Keywords

Artocarpus communis
Hedgehog signal
Hyptis suaveolens
Inhibitor
Natural products

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Arai, M. A., Uchida, K., Sadhu, S. K., Ahmed, F., Koyano, T., Kowithayakorn, T., & Ishibashi, M. (2015). Hedgehog inhibitors from Artocarpus communis and Hyptis suaveolens. Bioorganic and Medicinal Chemistry, 23(15), 4150-4154. https://doi.org/10.1016/j.bmc.2015.06.058

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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.",

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author = "Arai, {Midori A.} and Kyoko Uchida and Sadhu, {Samir K.} and Firoj Ahmed and Takashi Koyano and Thaworn Kowithayakorn and Masami Ishibashi",

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AU - Sadhu, Samir K.

AU - Ahmed, Firoj

AU - Koyano, Takashi

AU - Kowithayakorn, Thaworn

AU - Ishibashi, Masami

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