The aim of this study was to investigate the in vivo toxicities of some novel synthetic chalcones. Chalcone and four chalcone analogues 1a– d were evaluated using zebrafish embryos following antibody staining to visualize their morphological changes and muscle fiber alignment. Results showed that embryos treated with 3'-hydroxychalcone (compound 1b) displayed a high percentage of muscle defects (96.6%), especially myofibril misalignment. Ultrastructural analysis revealed that compound 1b-treated embryos displayed many muscle defect phenotypes, including breakage and collapse of myofibrils, reduced cell numbers, and disorganized thick (myosin) and thin (actin) filaments. Taken together, our results provide in vivo evidence of the myotoxic effects of the synthesized chalcone analogues on developing zebrafish embryos.
References
[1]
Mohamad, A.S.; Akhtar, M.N.; Zakaria, Z.A.; Perimal, E.K.; Khalid, S.; Mohd, P.A.; Khalid, M.H.; Israf, D.A.; Lajis, N.H.; Sulaiman, M.R. Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and thermal models of nociception in mice. Eur. J. Pharmacol. 2010, 647, 103–109, doi:10.1016/j.ejphar.2010.08.030.
[2]
Wu, J.; Lee, J.; Cai, Y.; Pan, Y.; Ye, F.; Zhang, Y.; Zhao, Y.; Yang, S.; Li, X.; Liang, G. Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents. J. Med. Chem. 2011, 54, 8110–8123, doi:10.1021/jm200946h.
[3]
Ajaiyeoba, E.O.; Ogbole, O.O.; Abiodun, O.O.; Ashidi, J.S.; Houghton, P.J.; Wright, C.W. Cajachalcone: An antimalarial compound from Cajanus cajan leaf extract. J. Parasitol. Res. 2013, 2013, 703781.
[4]
Ajiboye, T.O.; Yakubu, M.T.; Oladiji, A.T. Electrophilic and reactive oxygen species detoxification potentials of chalcone dimers is mediated by redox transcription factor Nrf-2. J. Biochem. Mol. Toxicol. 2013, doi:10.1002/jbt.21517.
[5]
Chen, Y.H.; Wang, W.H.; Wang, Y.H.; Lin, Z.Y.; Wen, C.C.; Chern, C.Y. Evaluation of anti-inflammatory effect of chalcone and chalcone analogues in a zebrafish model. Molecules 2013, 18, 2052–2060, doi:10.3390/molecules18022052.
[6]
Pan, Y.; Chen, Y.; Li, Q.; Yu, X.; Wang, J.; Zheng, J. The synthesis and evaluation of novel hydroxyl substituted chalcone analogs with in vitro anti-free radicals pharmacological activity and in vivo anti-oxidation activity in a free radical-injury Alzheimer’s model. Molecules 2013, 18, 1693–1703, doi:10.3390/molecules18021693.
[7]
Wei, H.; Zhang, X.; Wu, G.; Yang, X.; Pan, S.; Wang, Y.; Ruan, J. Chalcone derivatives from the fern Cyclosorus parasiticus and their anti-proliferative activity. Food Chem. Toxicol. 2013, 60, 147–152, doi:10.1016/j.fct.2013.07.045.
[8]
Sashidhara, K.V.; Kumar, A.; Kumar, M.; Sarkar, J.; Sinha, S. Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential anticancer agents. Bioorg. Med. Chem. Lett. 2010, 20, 7205–7211, doi:10.1016/j.bmcl.2010.10.116.
[9]
Fang, X.; Yang, B.; Cheng, Z.; Yang, M.; Su, N.; Zhou, L.; Zhou, J. Synthesis and antitumor activity of novel mustard-linked chalcones. Arch. Pharm. 2013, 346, 292–299, doi:10.1002/ardp.201200443.
[10]
Kamal, A.; Kashi Reddy, M.; Viswanath, A. The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs. Expert Opin. Drug Discov. 2013, 8, 289–304, doi:10.1517/17460441.2013.758630.
[11]
Neves, M.P.; Lima, R.T.; Choosang, K.; Pakkong, P.; de S?o José Nascimento, M.; Vasconcelos, M.H.; Pinto, M.; Silva, A.M.; Cidade, H. Synthesis of a natural chalcone and its prenyl analogs—Evaluation of tumor cell growth-inhibitory activities, and effects on cell cycle and apoptosis. Chem. Biodivers. 2012, 9, 1133–1143, doi:10.1002/cbdv.201100190.
[12]
Shin, S.Y.; Yoon, H.; Ahn, S.; Kim, D.W.; Kim, S.H.; Koh, D.; Lee, Y.H.; Lim, Y. Chromenylchalcones showing cytotoxicity on human colon cancer cell lines and in siloco docking with aurora kinases. Bioorg. Med. Chem. 2013, 21, 4250–4258, doi:10.1016/j.bmc.2013.04.086.
[13]
De Vasconcelos, A.; Campos, V.F.; Nedel, F.; Seixas, F.K.; Dellagostin, O.A.; Smith, K.R.; de Pereira, C.M.; Stefanello, F.M.; Collares, T.; Barschak, A.G. Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetylthiophene on human colon adenocarcinoma cells. Cell Biochem. Funct. 2013, 31, 289–297.
[14]
Forejtníková, H.; Lunerová, K.; Kubínová, R.; Jankovská, D.; Marek, R.; Such?, V.; Vondrácek, J. Chemoprotective and toxic potentials of synthetic and natural chalcones and dihydrochalcones in vitro. Toxicology 2005, 208, 81–93, doi:10.1016/j.tox.2004.11.011.
[15]
Waalkens-Berendsen, D.H.; Kuilman-Wahls, M.E.; B?r, A. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats. Regul. Toxicol. Pharmacol. 2004, 40, 74–79, doi:10.1016/j.yrtph.2004.05.007.
[16]
Ohkatsu, Y.; Satoh, T. Antioxidant and photo-antioxidant activities of chalcone derivatives. J. Jpn. Pet. Inst. 2008, 51, 298–308, doi:10.1627/jpi.51.298.
[17]
Karki, R.; Thapa, P.; Kang, M.J.; Jeong, T.C.; Nam, J.M.; Kim, H.L.; Na, Y.; Cho, W.J.; Kwon, Y.; Lee, E.S. Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl pyridines. Bioorg. Med. Chem. 2010, 18, 3066–3077, doi:10.1016/j.bmc.2010.03.051.
[18]
Kurniadewi, F.; Juliawaty, L.D.; Syah, Y.M.; Achmad, S.A.; Hakim, E.H.; Koyama, K.; Kinoshita, K.; Takahashi, K. Phenolic compounds from Cryptocarya konishii: Their cytotoxic and tyrosine kinase inhibitory properties. J. Nat. Med. 2010, 64, 121–125, doi:10.1007/s11418-009-0368-y.
Moorthy, N.S.H.N.; Singh, R.J.; Singh, H.P.; Gupta, S.D. Synthesis, biological evaluation and in silico metabolic and toxicity prediction of some flavanone derivatives. Chem. Pharm. Bull. 2006, 54, 1384–1390, doi:10.1248/cpb.54.1384.
[21]
Karki, R.; Thapa, P.; Yoo, H.Y.; Kadayat, T.M.; Park, P.H.; Na, Y.; Lee, E.; Jeon, K.H.; Cho, W.J.; Choi, H.; et al. Dihydroxylated 2,4,6-triphenyl pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study. Eur. J. Med. Chem. 2012, 49, 219–228, doi:10.1016/j.ejmech.2012.01.015.
[22]
Westerfield, M. The Zebrafish Book, 3rd ed. ed.; University of Oregon Press: Eugene, OR, USA, 1995.
[23]
Chen, Y.H.; Wang, Y.H.; Yu, T.H.; Wu, H.J.; Pai, C.W. Transgenic zebrafish line with over-expression of Hedgehog on the skin: A useful tool to screen Hedgehog-inhibiting compounds. Transgenic Res. 2009, 18, 855–864, doi:10.1007/s11248-009-9275-y.