Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases

Nobuo Suzuki; Masanori Somei; Azusa Seki; Toshio Sekiguchi; Yoshiaki Tabuchi; Hiroyuki Mishima; Yoichi Kase; Atsushi Kaminishi; Koji Yachiguchi; Kei-ichiro Kitamura; Yuji Oshima; Kazuichi Hayakawa; Sachiko Yano; Atsuhiko Hattori

doi:doi:10.11648/j.ajls.s.2015030302.16

Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases

Nobuo Suzuki, Masanori Somei, Azusa Seki, Toshio Sekiguchi, Yoshiaki Tabuchi, Hiroyuki Mishima, Yoichi Kase, Atsushi Kaminishi, Koji Yachiguchi, Kei-ichiro Kitamura, Yuji Oshima, Kazuichi Hayakawa, Sachiko Yano, Atsuhiko Hattori

Published in American Journal of Life Sciences (Volume 3, Issue 3-2)

Received: 16 February 2015 Accepted: 24 March 2015 Published: 6 May 2015

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Abstract

We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.

Published in	American Journal of Life Sciences (Volume 3, Issue 3-2) This article belongs to the Special Issue Biology and Medicine of Peptide and Steroid Hormones
DOI	10.11648/j.ajls.s.2015030302.16
Page(s)	31-38
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Tryptophan Derivatives, Osteoblasts, Osteoclasts, Scales, Bone Diseases, Ovariectomized Rats

References

[1]	J. Bereiter-Hahn, L. Zylberberg, “Regeneration of teleost fish scale,” Comp Biochem Physiol Part A, 1993, 105, pp. 625-641.
[2]	N. Suzuki, T. Suzuki, T. Kurokawa, “Suppression of osteoclastic activities by calcitonin in the scales of goldfish (freshwater teleost) and nibbler fish (seawater teleost),” Peptides, 2000, 21, pp. 115-124.
[3]	N. Suzuki, A. Hattori, “Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish,” J Pineal Res, 2002, 33, pp. 253-258.
[4]	H. Yoshikubo, N. Suzuki, K. Takemura, M. Hoso, S. Yashima, S. Iwamuro, Y. Takagi, M.J. Tabata, A. Hattori, “Osteoblastic activity and estrogenic response in the regenerating scale of goldfish, a good model of osteogenesis,” Life Sci, 2005, 76, pp. 2699-2709.
[5]	N. Suzuki, K. Kitamura, T. Nemoto, N. Shimizu, S. Wada, T. Kondo, M.J. Tabata, F. Sodeyama, K. Ijiri, A. Hattori, “Effect of vibration on osteoblastic and osteoclastic activities: analysis of bone metabolism using goldfish scale as a model for bone,” Adv Space Res, 2007, 40, pp. 1711-1721.
[6]	E. de Vrieze, F. Sharif, J.R. Metz, G. Flik, M.K. Richardson, “Matrix metalloproteinases in osteoclasts of ontogenetic and regenerating zebrafish scales,” Bone, 2011, 48, pp. 704-712.
[7]	N. Suzuki, J.A. Danks, Y. Maruyama, M. Ikegame, Y. Sasayama, A. Hattori, N. Nakamura, M.J. Tabata, T. Yamamoto, R. Furuya, K. Saijoh, H. Mishima, A.K. Srivastav, Y. Furusawa, T. Kondo, Y. Tabuchi, I. Takasaki, V.S. Chowdhury, K. Hayakawa, T.J. Martin, “Parathyroid hormone 1 (1-34) acts on the scales and involves calcium metabolism in goldfish,” Bone, 2011, 48, pp. 1186-1193.
[8]	K. Azuma, M. Kobayashi, M. Nakamura, N. Suzuki, S. Yashima, S. Iwamuro, M. Ikegame, T. Yamamoto, A. Hattori, “Two osteoclastic markers expressed in multinucleate osteoclasts of goldfish scales,” Biochem Biophys Res Commun, 2007, 362, pp. 594-600.
[9]	T.A. Thamamongood, R. Furuya, S. Fukuba, M. Nakamura, N. Suzuki, A. Hattori, “Expression of osteoblastic and osteoclastic genes during spontaneous regeneration and autotransplantation of goldfish scale: a new tool to study intramembranous bone regeneration,” Bone, 2012, 50, pp.1240-1249.
[10]	A. Berg, “Studies on the metabolism of calcium and strontium in freshwater fish I: relative contribution of direct and intestinal absorption,” Mem Ist Ital Idrobiol, 1968, 23, pp. 161-196.
[11]	Y. Mugiya, N. Watabe, “Studies on fish scale formation and resorption II: effect of estradiol on calcium homeostasis and skeletal tissue resorption in the goldfish, Carassius auratus, and the killifish, Fundulus heteroclitus,” Comp Biochem Physiol Part A, 1977, 57, pp. 197-202.
[12]	M. Somei, Y. Fukui, “Nucleophilic substitution reaction of 1-hydroxytryptophan and 1-hydroxytryptamine derivatives regioselective syntheses of 5-substituted derivatives of tryptophan and tryptamine” Heterocycles, 1993, 36, pp. 1859-1966.
[13]	J. Iwamoto, A. Seki, T. Takeda, Y. Sato, H. Yamada, J.K. Yeh, “Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats,” Exp Anim, 2006, 55, pp. 357-367.
[14]	N. Suzuki, A. Hattori, “Bisphenol A suppresses osteoclastic and osteoblastic activities in the cultured scales of goldfish,” Life Sci, 2003, 73, pp. 2237-2247.
[15]	N. Suzuki, M.J. Tabata, A. Kambegawa, A.K. Srivastav, A. Shimada, H. Takeda, M. Kobayashi, S. Wada, T. Katsumata, A. Hattori, “Tributyltin inhibits osteoblastic activity and disrupts calcium metabolism through an increase in plasma calcium and calcitonin levels in teleosts,” Life Sci, 2006, 78, pp. 2533-2541.
[16]	N. Suzuki, M. Yamamoto, K. Watanabe, A. Kambegawa, A. Hattori, “Both mercury and cadmium directly influence calcium homeostasis resulting from the suppression of scale bone cells: the scale is a good model for the evaluation of heavy metals in bone metabolism,” J Bone Miner Metab, 2004, 22, 439-446.
[17]	R, Rizzoli, J.Y. Reginster, “Adverse drug reactions to osteoporosis treatments,” Expert Rev Clin Pharmacol, 2011, 4, pp. 593-604.
[18]	T. Suda, N. Takahashi, N. Udagawa, E. Jimi, M.T. Gillespie, T.J. Martin, “Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families,” Endocr Rev, 1999, 20, pp. 345-357.
[19]	S.C. Manolagas, “Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis,” Endocr Rev, 2000, 21, pp. 115-137.
[20]	S.L. Teitelbaum, “Bone resorption by osteoclasts,” Science, 2000, 289, pp. 1504-1508.

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APA Style

Nobuo Suzuki, Masanori Somei, Azusa Seki, Toshio Sekiguchi, Yoshiaki Tabuchi, et al. (2015). Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. American Journal of Life Sciences, 3(3-2), 31-38. https://doi.org/10.11648/j.ajls.s.2015030302.16

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ACS Style

Nobuo Suzuki; Masanori Somei; Azusa Seki; Toshio Sekiguchi; Yoshiaki Tabuchi, et al. Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. Am. J. Life Sci. 2015, 3(3-2), 31-38. doi: 10.11648/j.ajls.s.2015030302.16

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AMA Style

Nobuo Suzuki, Masanori Somei, Azusa Seki, Toshio Sekiguchi, Yoshiaki Tabuchi, et al. Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. Am J Life Sci. 2015;3(3-2):31-38. doi: 10.11648/j.ajls.s.2015030302.16

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@article{10.11648/j.ajls.s.2015030302.16,
  author = {Nobuo Suzuki and Masanori Somei and Azusa Seki and Toshio Sekiguchi and Yoshiaki Tabuchi and Hiroyuki Mishima and Yoichi Kase and Atsushi Kaminishi and Koji Yachiguchi and Kei-ichiro Kitamura and Yuji Oshima and Kazuichi Hayakawa and Sachiko Yano and Atsuhiko Hattori},
  title = {Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases},
  journal = {American Journal of Life Sciences},
  volume = {3},
  number = {3-2},
  pages = {31-38},
  doi = {10.11648/j.ajls.s.2015030302.16},
  url = {https://doi.org/10.11648/j.ajls.s.2015030302.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030302.16},
  abstract = {We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.},
 year = {2015}
}

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TY  - JOUR
T1  - Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases
AU  - Nobuo Suzuki
AU  - Masanori Somei
AU  - Azusa Seki
AU  - Toshio Sekiguchi
AU  - Yoshiaki Tabuchi
AU  - Hiroyuki Mishima
AU  - Yoichi Kase
AU  - Atsushi Kaminishi
AU  - Koji Yachiguchi
AU  - Kei-ichiro Kitamura
AU  - Yuji Oshima
AU  - Kazuichi Hayakawa
AU  - Sachiko Yano
AU  - Atsuhiko Hattori
Y1  - 2015/05/06
PY  - 2015
N1  - https://doi.org/10.11648/j.ajls.s.2015030302.16
DO  - 10.11648/j.ajls.s.2015030302.16
T2  - American Journal of Life Sciences
JF  - American Journal of Life Sciences
JO  - American Journal of Life Sciences
SP  - 31
EP  - 38
PB  - Science Publishing Group
SN  - 2328-5737
UR  - https://doi.org/10.11648/j.ajls.s.2015030302.16
AB  - We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.
VL  - 3
IS  - 3-2
ER  -

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Author Information

Nobuo Suzuki

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Masanori Somei

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Azusa Seki

HAMRI Co. Ltd., Koga, Ibaraki 306-0101, Japan
Toshio Sekiguchi

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Yoshiaki Tabuchi

Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, Toyama 930-0194, Japan
Hiroyuki Mishima

Department of Medical Hygiene, Dental Hygiene Course, Kochi Gakuen College, Kochi, Kochi 780-0955, Japan
Yoichi Kase

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Atsushi Kaminishi

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Koji Yachiguchi

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan
Kei-ichiro Kitamura

Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kodatsuno, Ishikawa 920-0942, Japan
Yuji Oshima

Faculty of Agriculture, Kyushu University, Hakozaki, Fukuoka 812-8581, Japan
Kazuichi Hayakawa

Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma, Ishikawa 920-1192, Japan
Sachiko Yano

Japan Aerospace Exploration Agency, Tsukuba, Ibaraki 305-8505, Japan
Atsuhiko Hattori

Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Ichikawa, Chiba 272-0827, Japan

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APA Style

Nobuo Suzuki, Masanori Somei, Azusa Seki, Toshio Sekiguchi, Yoshiaki Tabuchi, et al. (2015). Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. American Journal of Life Sciences, 3(3-2), 31-38. https://doi.org/10.11648/j.ajls.s.2015030302.16

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ACS Style

Nobuo Suzuki; Masanori Somei; Azusa Seki; Toshio Sekiguchi; Yoshiaki Tabuchi, et al. Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. Am. J. Life Sci. 2015, 3(3-2), 31-38. doi: 10.11648/j.ajls.s.2015030302.16

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AMA Style

Nobuo Suzuki, Masanori Somei, Azusa Seki, Toshio Sekiguchi, Yoshiaki Tabuchi, et al. Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases. Am J Life Sci. 2015;3(3-2):31-38. doi: 10.11648/j.ajls.s.2015030302.16

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@article{10.11648/j.ajls.s.2015030302.16,
  author = {Nobuo Suzuki and Masanori Somei and Azusa Seki and Toshio Sekiguchi and Yoshiaki Tabuchi and Hiroyuki Mishima and Yoichi Kase and Atsushi Kaminishi and Koji Yachiguchi and Kei-ichiro Kitamura and Yuji Oshima and Kazuichi Hayakawa and Sachiko Yano and Atsuhiko Hattori},
  title = {Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases},
  journal = {American Journal of Life Sciences},
  volume = {3},
  number = {3-2},
  pages = {31-38},
  doi = {10.11648/j.ajls.s.2015030302.16},
  url = {https://doi.org/10.11648/j.ajls.s.2015030302.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030302.16},
  abstract = {We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.},
 year = {2015}
}

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TY  - JOUR
T1  - Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases
AU  - Nobuo Suzuki
AU  - Masanori Somei
AU  - Azusa Seki
AU  - Toshio Sekiguchi
AU  - Yoshiaki Tabuchi
AU  - Hiroyuki Mishima
AU  - Yoichi Kase
AU  - Atsushi Kaminishi
AU  - Koji Yachiguchi
AU  - Kei-ichiro Kitamura
AU  - Yuji Oshima
AU  - Kazuichi Hayakawa
AU  - Sachiko Yano
AU  - Atsuhiko Hattori
Y1  - 2015/05/06
PY  - 2015
N1  - https://doi.org/10.11648/j.ajls.s.2015030302.16
DO  - 10.11648/j.ajls.s.2015030302.16
T2  - American Journal of Life Sciences
JF  - American Journal of Life Sciences
JO  - American Journal of Life Sciences
SP  - 31
EP  - 38
PB  - Science Publishing Group
SN  - 2328-5737
UR  - https://doi.org/10.11648/j.ajls.s.2015030302.16
AB  - We recently developed an in vitro assay to study bone metabolism using fish scales that contain osteoblasts, osteoclasts, and calcified bone matrix, all of which are similar to those found in mammalian membrane bone. Using the fish scale assay, we previously reported that the functions of calcemic hormones such as calcitonin and parathyroid hormone in osteoblasts and osteoclasts were similar to those in mammals. Therefore, our fish scale in vitro assay system is suitable for the screening of potential bone-forming compounds. In an attempt to develop molecules that increase bone mass, novel tryptophan derivatives were synthesized and screened for effects on osteoblasts and osteoclasts using the fish scale model. As a result, novel tryptophan derivatives with the ability to possibly increase bone formation were identified, but they had no effect on osteoclast activity. Among the identified derivatives, (S)-(+)-N-acetyl-2,4,6-tribromo-5-methoxytryptophan methyl ester (BTryp) had the strongest activity on osteoblasts. The effect of this chemical on bone formation was confirmed in an ovariectomized (OVX) rat model of post-menopausal osteoporosis. Our data indicated that both trabecular bone mineral density and stress-strain index of the femoral metaphysis of BTryp-treated OVX rats were significantly higher than those of OVX rats. This study identified a bromotryptophan derivative that may have potential use in the treatment of bone diseases, such as osteoporosis.
VL  - 3
IS  - 3-2
ER  -

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