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
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Authors
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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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.
Keywords
Tryptophan Derivatives, Osteoblasts, Osteoclasts, Scales, Bone Diseases, Ovariectomized Rats
To cite this article
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, 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. doi: 10.11648/j.ajls.s.2015030302.16
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