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Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death

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Abstract

Nitensidine A is a guanidine alkaloid isolated from Pterogyne nitens, a common plant in South America. To gain insight into the biological activity of P. nitens-produced compounds, we examined herein their biological effects on osteoclasts, multinucleated giant cells that regulate bone metabolism by resorbing bone. Among four guanidine alkaloids (i.e., galegine, nitensidine A, pterogynidine, and pterogynine), nitensidine A and pterogynine exhibited anti-osteoclastic effects at 10 μM by reducing the number of osteoclasts on the culture plate whereas galegine and pterogynidine did not. The anti-osteoclastic activities of nitensidine A and pterogynine were exerted in a concentration-dependent manner, whereas nitensidine A exhibited an approximate threefold stronger effect than pterogynine (IC50 values: nitensidine A, 0.93 ± 0.024 μM; pterogynine, 2.7 ± 0.40 μM). In the present study, the anti-osteoclastic effects of two synthetic nitensidine A derivatives (nitensidine AT and AU) were also examined to gain insight into the structural features of nitensidine A that exert an anti-osteoclastic effect. The anti-osteoclastic effect of nitensidine A was greatly reduced by substituting the imino nitrogen atom in nitensidine A with sulfur or oxygen. According to the differences in chemical structures and anti-osteoclastic effects of the four guanidine alkaloids and the two synthetic nitensidine A derivatives, it is suggested that the number, binding site, and polymerization degree of isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their anti-osteoclastic effects.

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Acknowledgments

This study was supported by a Grant-in-Aid for Young Scientists (B) (JSPS KAKENHI Grant Number 22791786) and Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Number 24592822) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and Chubu University Grant A (23IM04A) and B (23IM02B and 24M01B) from Chubu University. The isolation of the guanidine alkaloids and synthesis of the nitensidine A derivatives were supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) as part of the Biota-FAPESP-The Biodiversity Virtual Institute Program (www.biotasp.org.br), Grant No. 03/02176-7, awarded to V.S.B.

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Authors and Affiliations

  1. Department of Applied Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi, 487-8501, Japan

    Yasuhiro Tajima, Hayato Murase, Kazuhiro Satake, Yuji Mitani & Hiroshi Nakagawa

  2. Department of Organic Chemistry, Institute of Chemistry, São Paulo State University, Araraquara, 14800-900, Brazil

    Luis Octavio Regasini & Vanderlan da Silva Bolzani

  3. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, 55128, Mainz, Germany

    Thomas Efferth

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  1. Yasuhiro Tajima
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  2. Hayato Murase
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  3. Kazuhiro Satake
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  4. Yuji Mitani
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  5. Luis Octavio Regasini
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  6. Vanderlan da Silva Bolzani
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  7. Thomas Efferth
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  8. Hiroshi Nakagawa
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Correspondence to Hiroshi Nakagawa.

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Tajima, Y., Murase, H., Satake, K. et al. Nitensidine A, a guanidine alkaloid from Pterogyne nitens, induces osteoclastic cell death. Cytotechnology 67, 585–592 (2015). https://doi.org/10.1007/s10616-013-9590-2

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  • DOI: https://doi.org/10.1007/s10616-013-9590-2

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