Chinese Journal of Organic Chemistry >
Synthesis and Antibiotic Activity Study of Pyridine Chalcone Derivatives against Methicillin-Resistant Staphylococcus aureus
Received date: 2016-10-11
Revised date: 2016-12-21
Online published: 2016-12-29
Supported by
Project supported by the National Natural Science Foundation of China (Nos. U1204206, 81501782) and the Education Department of Henan Province (No. 17A350004).
A series of pyridine chalcone derivatives were designed and synthesized. The structures were confirmed by 1H NMR, 13C NMR and HRMS. In vitro biological activity evaluation results showed that five of the compounds exhibited good biological activity against gram positive bacteria staphylococcus aureus (ATCC 29213). Further antibiotic activity of these five compounds against 11 clinical isolated methicillin-resistant staphylococcus aureus (MRSA) were evaluated. The results showed that four of the compounds exhibited good antibacterial activity against MRSA. (E)-2-Bromo-N-{4-[3-(pyridin-2-yl)- acryloyl]phenyl}acetamide (5k) showed the most effective activity (minimum inhibitory concentration, MIC=4 μg/mL). In terms of hemolytic activity evaluation, compound 5k showed virtually no toxicity even in 1000 μg/mL concentration. To sum up, pyridine chalcone 5k was potential for further antibiotic study as anti-MRSA agent.
Zhang En , Wang Mingming , Xu Shuaimin , Wang Shang , Zhao Di , Bai Pengyan , Cui Deyun , Hua Yonggang , Wang Ya'na , Qin Shangshang , Liu Hongmin . Synthesis and Antibiotic Activity Study of Pyridine Chalcone Derivatives against Methicillin-Resistant Staphylococcus aureus[J]. Chinese Journal of Organic Chemistry, 2017 , 37(4) : 959 -966 . DOI: 10.6023/cjoc201610016
[1] Jevons, M. P. Br. Med. J. 1961, 1, 124.
[2] Hamilton, G. L. A. Lab. Med. 2010, 41, 329.
[3] Deurenberg, R. H.; Nulens, E.; Valvatne, H.; Sebastian, S.; Driessen, C.; Craeghs, J.; De Brauwer, E.; Heising, B.; Kraat, Y. J.; Riebe, J.; Stals, F. S.; Trienekens, T. A.; Scheres, J.; Friedrich, A. W.; van Tiel, F. H.; Beisser, P. S.; Stobberingh, E. E. Emerging Infect. Dis. 2009, 15, 727.
[4] Kallen, A. J.; Mu, Y.; Bulens, S.; Reingold, A.; Petit, S.; Gershman, K.; Ray, S. M.; Harrison, L. H.; Lynfield, R.; Dumyati, G. JAMA, J. Am. Med. Assoc. 2010, 304, 641.
[5] Fridkin, S. K.; Hageman, J. C.; Morrison, M.; Sanza, L. T.; Como-Sabetti, K.; Jernigan, J. A.; Harriman, K.; Harrison, L. H.; Lynfield, R.; Farley, M. M. N. Engl. J. Med. 2005, 352, 1436.
[6] Cardo, D.; Horan, T.; Andrus, M.; Dembinski, M.; Edwards, J.; Peavy, G.; Tolson, J.; Wagner, D. Am. J. Infect. Control. 2004, 32, 470.
[7] Fridkin, S. K.; Yokoe, D. S.; Whitney, C. G.; Onderdonk, A.; Hooper, D. C. J. Clin. Microbiol. 1998, 36, 965.
[8] Rybak, M. J.; Abate, B. J.; Kang, S. L.; Ruffing, M. J.; Lerner, S. A.; Drusano, G. L. Antimicrob. Agents Chemother. 1999, 43, 1549.
[9] Nowakowska, Z. Eur. J. Med. Chem. 2007, 42, 125.
[10] Magiorakos, A. P.; Srinivasan, A.; Carey, R. B.; Carmeli, Y.; Falagas, M. E.; Giske, C. G.; Harbarth, S.; Hindler, J. F.; Kahlmeter, G.; Olsson-Liljequist, B.; Paterson, D. L.; Rice, L. B.; Stelling, J.; Struelens, M. J.; Vatopoulos, A.; Weber, J. T.; Monnet, D. L. Clin. Microbiol. Infect. 2012, 18, 268.
[11] Kluytmans, J.; Van Belkum, A.; Verbrugh, H. Clin. Microbiol. Rev. 1997, 10, 505.
[12] Patel, R. V.; Patel, P. K.; Kumari, P.; Rajani, D. P.; Chikhalia, K. H. Eur. J. Med. Chem. 2012, 53, 41.
[13] Chen, Z.-H.; Zheng, C.-J.; Sun, L.-P.; Piao, H.-R. Eur. J. Med. Chem. 2010, 45, 5739.
[14] Klevens, R. M.; Morrison, M. A.; Nadle, J.; Petit, S.; Gershman, K.; Ray, S.; Harrison, L. H.; Lynfield, R.; Dumyati, G.; Townes, J. M. JAMA, J. Am. Med. Assoc. 2007, 298, 1763.
[15] Zhang, Q.-R.; Xue, D.-Q.; He, P.; Shao, K.-P.; Chen, P.-J.; Gu, Y.-F.; Ren, J.-L.; Shan, L.-H.; Liu, H.-M. Bioorg. Med. Chem. Lett. 2014, 24, 1236.
[16] Chen, P.-J.; Yang, A.; Gu, Y.-F.; Zhang, X.-S.; Shao, K.-P.; Xue, D.-Q.; He, P.; Jiang, T.-F.; Zhang, Q.-R.; Liu, H.-M. Bioorg. Med. Chem. Lett. 2014, 24, 2741.
[17] Nielsen, S. F.; Larsen, M.; Boesen, T.; Schønning, K.; Kromann, H. J. Med. Chem. 2005, 48, 2667.
[18] Stringer, J. R.; Bowman, M. D.; Weisblum, B.; Blackwell, H. E. ACS Comb. Sci. 2011, 13, 175.
[19] Joshi, A. S.; Li, X. C.; Nimrod, A. C.; ElSohly, H. N.; Walker, L. A.; Clark, A. M. Planta Med. 2001, 67, 186.
[20] Fu, D.-J.; Zhang, S.-Y.; Liu, Y.-C.; Yue, X.-X.; Liu, J.-J.; Song, J.; Zhao, R.-H.; Li, F.; Sun, H.-H.; Zhang, Y.-B.; Liu, H.-M. Med. Chem. Commun. 2016, 7, 1664.
[21] Fu, D.-J.; Zhang, S.-Y.; Liu, Y.-C.; Zhang, L.; Liu, J.-J.; Song, J.; Zhao, R.-H.; Li, F.; Sun, H.-H.; Liu, H.-M.; Zhang, Y.-B. Bioorg. Med. Chem. Lett. 2016, 26, 3918.
[22] Ling, L. L.; Schneider, T.; Peoples, A. J.; Spoering, A. L.; Engels, I.; Conlon, B. P.; Mueller, A.; Schaberle, T. F.; Hughes, D. E.; Epstein, S.; Jones, M.; Lazarides, L.; Steadman, V. A.; Cohen, D. R.; Felix, C. R.; Fetterman, K. A.; Millett, W. P.; Nitti, A. G.; Zullo, A. M.; Chen, C.; Lewis, K. Nature 2015, 517, 455.
[23] Ghosh, C.; Manjunath, G. B.; Akkapeddi, P.; Yarlagadda, V.; Hoque, J.; Uppu, D. S.; Konai, M. M.; Haldar, J. J. Med. Chem. 2014, 57, 1428.
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