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Biochemistry Research International Volume 2017 ,2017-06-21
Synthesis and Evaluation of In Vitro Antibacterial and Antitumor Activities of Novel N,N-Disubstituted Schiff Bases
Research Article
Heng Luo 1 , 2 , 3 Yu-fen Xia 2 , 4 Bao-fei Sun 4 Li-rong Huang 2 , 3 Xing-hui Wang 2 , 3 Hua-yong Lou 2 , 3 Xu-hui Zhu 1 Wei-dong Pan 2 , 3 Xiao-dong Zhang 1
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DOI:10.1155/2017/6257240
Received 2016-11-29, accepted for publication 2017-04-20, Published 2017-04-20
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摘要

To get inside the properties of N,N-disubstituted Schiff bases, we synthesized three high-yielding benzaldehyde Schiff bases. We used the reaction between salicylaldehyde and different diamine compounds, including diamine, ethanediamine, and o-phenylenediamine, determining the structure of obtained molecules by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectroscopy. We thus evaluated the microbicidal and antitumor activity of these compounds, showing that salicylaldehyde-hydrazine hydrate Schiff base (compound 1a) significantly inhibited the growth of S. aureus; salicylaldehyde-o-phenylenediamine Schiff base (compound 1c) displayed a strong capability to inhibit the proliferation of leukemia cell lines K562 and HEL. Moreover, we observed that the antibacterial action of 1a might be associated with the regulation of the expression of key virulence genes in S. aureus. Compound 1c resulted in a strong apoptotic activity against leukemia cells, also affecting the cell cycle distribution. Overall, our novel N,N-disubstituted Schiff bases possess unique antibacterial or antitumor activities that exhibit the potent application prospect in prophylactic or therapeutic interventions, providing new insights for developing new antibacterial and anticancer chemical agents.

授权许可

Copyright © 2017 Heng Luo et al. 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

The synthesis and chemical structure of salicylaldehyde-hydrazine hydrate Schiff base (1a).

The synthesis and chemical structure of salicylaldehyde-ethylenediamine Schiff base (1b).

The synthesis and chemical structure of salicylaldehyde-o-phenylenediamine Schiff base (1c).

Evaluation of the inhibitory activity of salicylaldehyde-hydrazine hydrate Schiff base (1a) against S. aureus in vitro. Various concentrations of compound 1a were added to 96-well microculture plates containing the S. aureus strain ATCC 25923 at concentration of 105 CFU/mL in Luria Broth. The absorbance of every well at 450 nm was assayed in an ELISA plate reader after shaking on a vibrating platform at 37°C for 8 h. The inhibition ratio (%) was determined as reported in Materials and Methods. Values are mean ± standard deviation of three independent experiments.

The compound 1a affects S. aureus virulence genes expression in vitro. (a) Fold changes of the expression of the related virulence genes were determined by real-time RT-PCR. (b) The transcript expression level of the genes was investigated using semiquantitative RT-PCR. Data are normalized to the transcript abundance of gyrB gene. Values are mean ± standard deviation of three independent experiments. P∗∗<0.01.

Antitumor activity in vitro of compounds 1a, 1b, and 1c assayed at the concentration of 5 μmol/L. Cancer cell survival was assayed by MTT method. The results represent the mean ± standard deviation of three independent experiments. P∗∗<0.01.

Concentration-inhibition curves of the active compounds against the proliferation of prostate ((a) PC3 and BPH1 cells), melanoma ((b) WM9 cells), and leukemia ((c) K562 and HEL cells) cell lines in vitro. Different concentrations of tested compounds were added to 96-well microculture plates and cells were incubated for 48 h at 37°C. The inhibition ratio (%) was calculated as described in Materials and Methods.

Concentration-inhibition curves of the active compounds against the proliferation of prostate ((a) PC3 and BPH1 cells), melanoma ((b) WM9 cells), and leukemia ((c) K562 and HEL cells) cell lines in vitro. Different concentrations of tested compounds were added to 96-well microculture plates and cells were incubated for 48 h at 37°C. The inhibition ratio (%) was calculated as described in Materials and Methods.

Concentration-inhibition curves of the active compounds against the proliferation of prostate ((a) PC3 and BPH1 cells), melanoma ((b) WM9 cells), and leukemia ((c) K562 and HEL cells) cell lines in vitro. Different concentrations of tested compounds were added to 96-well microculture plates and cells were incubated for 48 h at 37°C. The inhibition ratio (%) was calculated as described in Materials and Methods.

Concentration-inhibition curves of the active compounds against the proliferation of prostate ((a) PC3 and BPH1 cells), melanoma ((b) WM9 cells), and leukemia ((c) K562 and HEL cells) cell lines in vitro. Different concentrations of tested compounds were added to 96-well microculture plates and cells were incubated for 48 h at 37°C. The inhibition ratio (%) was calculated as described in Materials and Methods.

Evaluation of the apoptosis induced by the three N,N-disubstituted Schiff bases on two leukemia cell lines (a) and two prostate cell lines (b) using the annexin V-FITC/IP staining, followed by flow cytometer analysis. (c) Comparison of the apoptosis induced by compounds 1a, 1b, and 1c. Histograms represent annexin V-FITC/IP stained cells cultured in the presence of 5 μmol/L of tested compounds. Data showed the percentage of late induced apoptotic cells (upper right quadrant) and represent the mean ± standard deviation of three independent experiments, each performed in duplicate. P∗<0.05; P∗∗<0.01.

Evaluation of the apoptosis induced by the three N,N-disubstituted Schiff bases on two leukemia cell lines (a) and two prostate cell lines (b) using the annexin V-FITC/IP staining, followed by flow cytometer analysis. (c) Comparison of the apoptosis induced by compounds 1a, 1b, and 1c. Histograms represent annexin V-FITC/IP stained cells cultured in the presence of 5 μmol/L of tested compounds. Data showed the percentage of late induced apoptotic cells (upper right quadrant) and represent the mean ± standard deviation of three independent experiments, each performed in duplicate. P∗<0.05; P∗∗<0.01.

Evaluation of the apoptosis induced by the three N,N-disubstituted Schiff bases on two leukemia cell lines (a) and two prostate cell lines (b) using the annexin V-FITC/IP staining, followed by flow cytometer analysis. (c) Comparison of the apoptosis induced by compounds 1a, 1b, and 1c. Histograms represent annexin V-FITC/IP stained cells cultured in the presence of 5 μmol/L of tested compounds. Data showed the percentage of late induced apoptotic cells (upper right quadrant) and represent the mean ± standard deviation of three independent experiments, each performed in duplicate. P∗<0.05; P∗∗<0.01.

Effects of the three N,N-disubstituted Schiff bases on the cell cycle of leukemia and prostate cells. K562 and HEL leukemia cell lines (a) and one prostate cancer cell line PC3 and prostate mesenchymal cell line BPH1 (b) were used for assaying the cell cycle change by the treating with the active compounds, and then, the date were analyzed to obtain the more intuitive results (c and d). Compounds 1a, 1b, and 1c were assayed at the concentration of 20 μmol/L. Data represent the mean ± standard deviation of three independent experiments. P∗<0.05; P∗∗<0.01.

Effects of the three N,N-disubstituted Schiff bases on the cell cycle of leukemia and prostate cells. K562 and HEL leukemia cell lines (a) and one prostate cancer cell line PC3 and prostate mesenchymal cell line BPH1 (b) were used for assaying the cell cycle change by the treating with the active compounds, and then, the date were analyzed to obtain the more intuitive results (c and d). Compounds 1a, 1b, and 1c were assayed at the concentration of 20 μmol/L. Data represent the mean ± standard deviation of three independent experiments. P∗<0.05; P∗∗<0.01.

Effects of the three N,N-disubstituted Schiff bases on the cell cycle of leukemia and prostate cells. K562 and HEL leukemia cell lines (a) and one prostate cancer cell line PC3 and prostate mesenchymal cell line BPH1 (b) were used for assaying the cell cycle change by the treating with the active compounds, and then, the date were analyzed to obtain the more intuitive results (c and d). Compounds 1a, 1b, and 1c were assayed at the concentration of 20 μmol/L. Data represent the mean ± standard deviation of three independent experiments. P∗<0.05; P∗∗<0.01.

Effects of the three N,N-disubstituted Schiff bases on the cell cycle of leukemia and prostate cells. K562 and HEL leukemia cell lines (a) and one prostate cancer cell line PC3 and prostate mesenchymal cell line BPH1 (b) were used for assaying the cell cycle change by the treating with the active compounds, and then, the date were analyzed to obtain the more intuitive results (c and d). Compounds 1a, 1b, and 1c were assayed at the concentration of 20 μmol/L. Data represent the mean ± standard deviation of three independent experiments. P∗<0.05; P∗∗<0.01.

通讯作者

1. Wei-dong Pan.State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guizhou 550014, China, gmc.edu.cn;Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou 550014, China, cas.cn.wdpan@163.com
2. Xiao-dong Zhang.Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100043, China, ccmu.edu.cn.zxd581@263.net

推荐引用方式

Heng Luo,Yu-fen Xia,Bao-fei Sun,Li-rong Huang,Xing-hui Wang,Hua-yong Lou,Xu-hui Zhu,Wei-dong Pan,Xiao-dong Zhang. Synthesis and Evaluation of In Vitro Antibacterial and Antitumor Activities of Novel N,N-Disubstituted Schiff Bases. Biochemistry Research International ,Vol.2017(2017)

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参考文献
[1] J. V. Ragavendran, D. Sriram, S. K. Patel, I. V. Reddy. et al.(2007). Design and synthesis of anticonvulsants from a combined phthalimide-GABA-anilide and hydrazone pharmacophore. European Journal of Medicinal Chemistry.42(2):146-151. DOI: 10.1016/j.jare.2010.05.004.
[2] C. M. Da Silva, D. L. Da Silva, L. V. Modolo, R. B. Alves. et al.(2011). Schiff bases: a short review of their antimicrobial activities. Journal of Advanced Research.2(1):1-8. DOI: 10.1016/j.jare.2010.05.004.
[3] L. Xia, Y.-F. Xia, L.-R. Huang, X. Xiao. et al.(2015). Benzaldehyde Schiff bases regulation to the metabolism, hemolysis, and virulence genes expression in vitro and their structure-microbicidal activity relationship. European Journal of Medicinal Chemistry.97:83-93. DOI: 10.1016/j.jare.2010.05.004.
[4] L. Huang, H. Luo, Q. Li, D. Wang. et al.(2015). Pentacyclic triterpene derivatives possessing polyhydroxyl ring A inhibit Gram-positive bacteria growth by regulating metabolism and virulence genes expression. European Journal of Medicinal Chemistry.95:64-75. DOI: 10.1016/j.jare.2010.05.004.
[5] L. B. Rice. (2006). Unmet medical needs in antibacterial therapy. Biochemical Pharmacology.71(7):991-995. DOI: 10.1016/j.jare.2010.05.004.
[6] F. Baquero. (1997). Gram-positive resistance: challenge for the development of new antibiotics. Journal of Antimicrobial Chemotherapy.39:1-6. DOI: 10.1016/j.jare.2010.05.004.
[7] D. R. Long, J. Mead, J. M. Hendricks, M. E. Hardy. et al.(2013). 18-glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrobial Agents and Chemotherapy.57(1):241-247. DOI: 10.1016/j.jare.2010.05.004.
[8] M. N. Alekshun, S. B. Levy. (2007). Molecular mechanisms of antibacterial multidrug resistance. Cell.128(6):1037-1050. DOI: 10.1016/j.jare.2010.05.004.
[9] L.-R. Huang, X.-J. Hao, Q.-J. Li, D.-P. Wang. et al.(2016). 18-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents. Journal of Natural Products.79(4):721-731. DOI: 10.1016/j.jare.2010.05.004.
[10] N. Ergenc, N. S. Gunay. (1998). Synthesis and antidepressant evaluation of new 3-phenyl-5-sulfonamidoindole derivatives. European Journal of Medicinal Chemistry.33(2):143-148. DOI: 10.1016/j.jare.2010.05.004.
[11] P. Vicini, F. Zani, P. Cozzini, I. Doytchinova. et al.(2002). Hydrazones of 1,2-benzisothiazole hydrazides: synthesis, antimicrobial activity and QSAR investigations. European Journal of Medicinal Chemistry.37(7):553-564. DOI: 10.1016/j.jare.2010.05.004.
[12] Z. Guo, R. Xing, S. Liu, Z. Zhong. et al.(2007). Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan. Carbohydrate Research.342(10):1329-1332. DOI: 10.1016/j.jare.2010.05.004.
[13] J. Jayabharathi, A. Thangamani, M. Padmavathy, B. Krishnakumar. et al.(2007). Synthesis and microbial evaluation of novel N(1)-Arilidene-N(2)-t(3)- methyl-r(2), c(6)-diaryl-piperidin-4-one azine derivatives. Medicinal Chemistry Research.15(7-8):431-442. DOI: 10.1016/j.jare.2010.05.004.
[14] H.-Z. Zhang, J. Drewe, B. Tseng, S. Kasibhatla. et al.(2004). Discovery and SAR of indole-2-carboxylic acid benzylidene-hydrazides as a new series of potent apoptosis inducers using a cell-based HTS assay. Bioorganic and Medicinal Chemistry.12(13):3649-3655. DOI: 10.1016/j.jare.2010.05.004.
[15] S. Sharma, A. Jain, A. Aggarwal, N. Gill. et al.(2012). Synthesis, Characterization and pharmacological evaluation of novel schiff bases of imide moiety. Journal of Medical Sciences.12(3):61-69. DOI: 10.1016/j.jare.2010.05.004.
[16] A. O. De Souza, F. C. S. Galetti, C. L. Silva, B. Bicalho. et al.(2007). Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Quimica Nova.30(7):1563-1566. DOI: 10.1016/j.jare.2010.05.004.
[17] A. D. Kennedy, J. B. Wardenburg, D. J. Gardner, D. Long. et al.(2010). Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infection in a mouse model. Journal of Infectious Diseases.202(7):1050-1058. DOI: 10.1016/j.jare.2010.05.004.
[18] T. K. Nygaard, K. B. Pallister, P. Ruzevich, S. Griffith. et al.(2010). Saer binds a consensus sequence within virulence Gene promoters to advance USA300 pathogenesis. Journal of Infectious Diseases.201(2):241-254. DOI: 10.1016/j.jare.2010.05.004.
[19] G. Bringmann, M. Dreyer, J. H. Faber, P. W. Dalsgaard. et al.(2004). Ancistrotanzanine C and related 5,1′- and 7,3′-coupled naphthylisoquinoline alkaloids from Ancistrocladus tanzaniensis. Journal of Natural Products.67(5):743-748. DOI: 10.1016/j.jare.2010.05.004.
[20] H. Schiff. (1864). Mittheilungen aus dem Universitätslaboratorium in Pisa: Eine neue Reihe organischer Basen. Justus Liebigs Annalen der Chemie.131(1):118-119. DOI: 10.1016/j.jare.2010.05.004.
[21] E. J. Smith, L. Visai, S. W. Kerrigan, P. Speziale. et al.(2011). The Sbi protein is a multifunctional immune evasion factor of. Infection and Immunity.79(9):3801-3809. DOI: 10.1016/j.jare.2010.05.004.
[22] P. Przybylski, A. Huczynski, K. Pyta, B. Brzezinski. et al.(2009). Biological properties of schiff bases and azo derivatives of phenols. Current Organic Chemistry.13(2):124-148. DOI: 10.1016/j.jare.2010.05.004.
[23] S. A. M. El-Hawash, A. E. Abdel Wahab, M. A. El-Demellawy. (2006). Cyanoacetic acid hydrazones of 3-(and 4-)acetylpyridine and some derived ring systems as potential antitumor and anti-HCV agents. Archiv der Pharmazie.339(1):14-23. DOI: 10.1016/j.jare.2010.05.004.
[24] CL. Dhar DNTaploo. (1982). Schiff bases and their applications. DOI: 10.1016/j.jare.2010.05.004.
[25] A. R. Todeschini, A. L. P. de Miranda, K. C. M. da Silva, S. C. Parrini. et al.(1998). Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives. European Journal of Medicinal Chemistry.33(3):189-199. DOI: 10.1016/j.jare.2010.05.004.
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