Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases
American Journal of Life Sciences
Volume 3, Issue 3-2, May 2015, Pages: 31-38
Received: Feb. 16, 2015;
Accepted: Mar. 24, 2015;
Published: May 6, 2015
Views 3899 Downloads 111
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
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.
Novel Tryptophan Derivatives as Potentially Effective Therapeutic Drugs to Treat Bone Diseases, American Journal of Life Sciences. Special Issue:Biology and Medicine of Peptide and Steroid Hormones.
Vol. 3, No. 3-2,
2015, pp. 31-38.
J. Bereiter-Hahn, L. Zylberberg, “Regeneration of teleost fish scale,” Comp Biochem Physiol Part A, 1993, 105, pp. 625-641.
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.
N. Suzuki, A. Hattori, “Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish,” J Pineal Res, 2002, 33, pp. 253-258.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
N. Suzuki, A. Hattori, “Bisphenol A suppresses osteoclastic and osteoblastic activities in the cultured scales of goldfish,” Life Sci, 2003, 73, pp. 2237-2247.
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.
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.
R, Rizzoli, J.Y. Reginster, “Adverse drug reactions to osteoporosis treatments,” Expert Rev Clin Pharmacol, 2011, 4, pp. 593-604.
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.
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.
S.L. Teitelbaum, “Bone resorption by osteoclasts,” Science, 2000, 289, pp. 1504-1508.