Crystal Structures, ct-DNA/BSA Binding Properties and Antibacterial Activities of Halogenated Pyridyl Hydrazones

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摘要 Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chlo-ropyridine-2-formyl acylhydrazone (C13H9Cl2N3O, 3a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone (C13H9BrClN3O, 3b) and 4-iodobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone (C13H9ClIN3O, 3c), have been synthesized and characterized by elemental analysis, IR, 1H NMR, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that 3a～3c crystallize in monoclinic with space group Cc. The units of 3a～3c were linked by intermolecular N–H···X (X = Cl, Br, I) hydrogen bonds into 2D layered structures, which were further extended into 3D networks by a series of π-π stacking interactions. Thermogravimetric analysis showed that all of them possessed higher thermal stabilities. The reactivities toward calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) of 3a～3c were investigated by UV-vis and fluorescent spectroscopy as well as molecular docking simulation. Both theoretical and experimental results indicated that 3a～3c bound to ct-DNA in the mode of minor groove binding, and interacted with BSA through the hydrophobic cavity near TRP213. Besides, the orders of binding affinities of 3a～3c to ct-DNA and BSA were both 3c > 3b > 3a, which were the same as that of antibacterial activities. Thus, the interactions of iodinated acylhydrazone with biological targets were stronger than that of chlorinated and brominated acylhydrazones, which provided a representative case for halogenation of lead compounds in rational drug design.

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	廖庚晖
	刘向荣
	赵顺省
	杨再文
	杨征

关键词 ： acylhydrazone, crystal structure, thermal stability, ct-DNA, BSA, antibacterial activity

Abstract：

Three new halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4-chlo-ropyridine-2-formyl acylhydrazone (C13H9Cl2N3O, 3a), 4-bromobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone (C13H9BrClN3O, 3b) and 4-iodobenzaldehyde-4-chloropyridine-2-formyl acylhydrazone (C13H9ClIN3O, 3c), have been synthesized and characterized by elemental analysis, IR, 1H NMR, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that 3a～3c crystallize in monoclinic with space group Cc. The units of 3a～3c were linked by intermolecular N–H···X (X = Cl, Br, I) hydrogen bonds into 2D layered structures, which were further extended into 3D networks by a series of π-π stacking interactions. Thermogravimetric analysis showed that all of them possessed higher thermal stabilities. The reactivities toward calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) of 3a～3c were investigated by UV-vis and fluorescent spectroscopy as well as molecular docking simulation. Both theoretical and experimental results indicated that 3a～3c bound to ct-DNA in the mode of minor groove binding, and interacted with BSA through the hydrophobic cavity near TRP213. Besides, the orders of binding affinities of 3a～3c to ct-DNA and BSA were both 3c > 3b > 3a, which were the same as that of antibacterial activities. Thus, the interactions of iodinated acylhydrazone with biological targets were stronger than that of chlorinated and brominated acylhydrazones, which provided a representative case for halogenation of lead compounds in rational drug design.

Key words： acylhydrazone crystal structure thermal stability ct-DNA BSA antibacterial activity

收稿日期: 2019-06-20 出版日期: 2020-03-12

基金资助:This work was supported by the National Natural Science Foundation of China (Nos. 21073139 and 21373158) and Science and Technology on Combustion and Explosion Laboratory Foundation of Shaanxi (No. 6142603010301)

通讯作者: liuxiangrongxk@163.com E-mail: liuxiangrongxk@163.com

引用本文:

廖庚晖;刘向荣;赵顺省;杨再文;杨征. Crystal Structures, ct-DNA/BSA Binding Properties and Antibacterial Activities of Halogenated Pyridyl Hydrazones[J]. 结构化学, 2020, 39(3): 467-484.
LIAO Geng-Hui;LIU Xiang-Rong;ZHAO Shun-Sheng;YANG Zai-Wen;YANG Zheng . Crystal Structures, ct-DNA/BSA Binding Properties and Antibacterial Activities of Halogenated Pyridyl Hydrazones. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2020, 39(3): 467-484.

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http://manu30.magtech.com.cn/jghx/CN/ 或 http://manu30.magtech.com.cn/jghx/CN/Y2020/V39/I3/467

REFERENCES
(1) Carcelli, M.; Rogolino, D.; Gatti, A.; De Luca, L.; Sechi, M.; Kumar, G.; White, S. W.; Stevaert, A.; Naesens, L. N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes. Sci. Rep. 2016, 6, 31500.
(2) Badiger, D. S.; Hunoor, R. S.; Patil, B. R.; Vadavi, R. S.; Mangannavar, C. V.; Muchchandi, I. S.; Gudasi, K. B. Synthesis, physico-chemical characterization and antimicrobial activities of 3-methoxysalicylaldehyde-2-aminobenzoylhydrazone and its transition metal complexes. J. Mol. Struct. 2012, 1019, 159–165.
(3) Congiu, C.; Onnis, V. Synthesis and biological evaluation of novel acylhydrazone derivatives as potential antitumor agents. Bioorg. Med. Chem. 2013, 21, 6592–6599.
(4) Liu, Y. C.; Zhang, K. J.; Lei, R. X.; Liu, J. N.; Zhou, T. L.; Yang, Z. Y. DNA-binding and anti-oxidation properties of binuclear lanthanide(III) complexes of 8-hydroxyquinoline-7-carbaldehyde-(isonicotinyl)hydrazone. J. Coord. Chem. 2012, 65, 2041– 2054.
(5) Mazur, L.; Jarzembska, K. N.; Kamiński, R.; Hoser, A. A.; Madsen, A. Ø.; Pindelska, E.; Zielińska-Pisklak, M. Crystal structures and thermodynamic properties of polymorphs and hydrates of selected 2-pyridinecarboxaldehyde hydrazones. Cryst. Growth. Des. 2016, 16, 3101–3112.
(6) Ranga, R.; Sharma, V.; Kumar, V. New thiazolidinyl analogs containing pyridine ring: synthesis, biological evaluation and QSAR studies. Med. Chem. Res. 2013, 22, 1538–1548.
(7) Hallengren, B.; Hegarty, M. P.; Forsgren, A.; Ericson, L. E.; Melander, A. 3,4-Dihydroxypyridine: a potential antithyroid drug. Acta Endocrinologica 1987, 114, 305–307.
(8) Balzarini, J.; Stevens, M.; De Clercq, E.; Schols, D.; Pannecouque, C. Pyridine N-oxide derivatives: unusual anti-HIV compounds with multiple mechanisms of antiviral action. J. Antimicrob. Chemoth. 2005, 55, 135–138.
(9) Hosni, H.; Abdulla, M. Anti-inflammatory and analgesic activities of some newly synthesized pyridinedicarbonitrile and benzopyranopyridine derivatives. Acta Pharm. 2008, 58, 175–186.
(10) Bera, P.; Brandão, P.; Mondal, G.; Jana, H.; Jana, A.; Santra, A.; Bera, P. Synthesis of a new pyridinyl thiazole ligand with hydrazone moiety and its cobalt(III) complex: X-ray crystallography, in vitro, evaluation of antibacterial activity. Polyhedron 2017, 134, 230–237.
(11) Ren, J.; He, Y.; Chen, W. H.; Chen, T. T.; Wang, G.; Wang, Z.; Xu, Z. J.; Luo, X. M.; Zhu, W. L.; Jiang, H. L.; Shen, J. S.; Xu, Y. C. Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors. J. Med. Chem. 2014, 57, 3588–3593.
(12) Byeon, S. R.; Lee, J. H.; Sohn, J. H.; Kim, D. C.; Shin, K. J.; Yoo, K. H.; Mook-Jung, I.; Lee, W. K.; Kim, D. J. Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Aβ fibril formation. Bioorg. Med. Chem. Lett. 2007, 17, 1466–1470.
(13) Fais, A.; Kumar, A.; Medda, R.; Pintus, F.; Delogu, F.; Matos, M. J.; Era, B.; Delogu, G. L. Synthesis, molecular docking and cholinesterase inhibitory activity of hydroxylated 2-phenylbenzofuran derivatives. Bioorg. Chem. 2019, 84, 302–308.
(14) Zhang, J. P.; Li, X. Y.; Dong, Y. W.; Qin, Y. G.; Li, X. L.; Song, B. A.; Yang, X. L. Synthesis and biological evaluation of 4-methyl-1,2,3-thiadiazole-5-carboxaldehyde benzoyl hydrazone derivatives. Chin. Chem. Lett. 2017, 28, 1238–1242.
(15) Xue, F.; Xie, C. Z.; Zhang, Y. W.; Qiao, Z.; Qiao, X.; Xu, J. Y.; Yan, S. P. Two new dicopper(II) complexes with oxamido-bridged ligand: synthesis, crystal structures, DNA binding/cleavage and BSA binding activity. J. Inorg. Biochem. 2012, 115, 78–86.
(16) Qi, S.; Li, Y. H.; Yang, Y.; He, Y. T.; Cai, J.; Lin, S. W.; Yue, S. M. Syntheses, crystal structures and DNA-binding properties of Zn(II), Ni(II) and Co(II) compounds containing thiazole derivatives. Chin. J. Struct. Chem. 2018, 37, 1945–1959.
(17) Bi, S. Y.; Zhou, H. F.; Wu, J.; Sun, X. Y. Micronomicin/tobramycin binding with DNA: fluorescence studies using of ethidium bromide as a probe and molecular docking analysis. J. Biomol. Struct. Dyn. 2019, 37, 1464–1476.
(18) Tian, F. F.; Jiang, F. L.; Han, X. L.; Xiang, C.; Ge, Y. S.; Li, J. H.; Zhang, Y.; Li, R.; Ding, X. L.; Liu, Y. Synthesis of a novel hydrazone derivative and biophysical studies of its interactions with bovine serum albumin by spectroscopic, electrochemical, and molecular docking methods. J. Phys. Chem. B. 2010, 114, 14842–14853.
(19) Siemens: SMART and SAINT. Area detector control and integration software. Siemens analytical X-ray systems inc.; Madison, Wisconsin, USA: 1996.
(20) Sheldrick, G. M. SADABS, Program for Empirical Absorption Correction of Area Detector Data. University of Göttingen; Germany 1996.
(21) Sheldrick, G. M. SHELXS-97, Program for the Solution of Crystal Structures. University of Göttingen, Germany 1997.
(22) Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal Structures. University of Göttingen, Germany 1997.
(23) Merril, C. R.; Goldman, D. S.; Sedman, S. A.; Ebert, M. H. Ultrasensitive stain for proteins in polyacrylamide gels shows regional variation in cerebrospinal fluid proteins. Science 1981, 211, 1437–1438.
(24) Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 2010, 30, 2785–2791.
(25) Dassault Systèmes BIOVIA, Discovery studio client, 4.5.0, San Diego: Dassault Systèmes 2015.
(26) Ainscough, E. W.; Brodie, A. M.; Dobbs, A. J.; Ranford, J. D.; Waters, J. M. Antitumour copper(II) salicylaldehyde benzoylhydrazone (H2sb) complexes: physicochemical properties and the single-crystal X-ray structures of [{Cu(H2sb)(CCl3CO2)2}2] and [{Cu(Hsb)(ClO4)(C2H5OH)2]. Inorg. Chim. Acta 1998, 267, 27–38.
(27) Singh, P.; Singh, A. K.; Singh, V. P. Synthesis, structural and corrosion inhibition properties of some transition metal(II) complexes with o-hydroxyacetophenone-2-thiophenoyl hydrazone. Polyhedron 2013, 65, 73–81.
(28) Zhang, X. H.; Chen, S.; Min, Y. Q.; Qi, G. R. Synthesis of novel bisphenol containing phthalazinone and azomethine moieties and thermal properties of cured diamine/bisphenol/DGEBA polymers. Polymer 2006, 47, 1785–1795.
(29) Bravo-Gómez, M. E.; Campero-Peredo, C.; García-Conde, D.; Mosqueira-Santillán, M. J.; Serment-Guerrero, J.; Ruiz-Azuara, L. DNA-binding mode of antitumoral copper compounds (Casiopeinas®;) and analysis of its biological meaning. Polyhedron 2015, 102, 530–538.
(30) Mistri, S.; Puschmann, H.; Manna, S. C. DNA/protein binding, cytotoxicity and catecholase activity studies of a piperazinyl moiety ligand based nickel(II) complex. Polyhedron 2016, 115, 155–163.
(31) Liu, K.; Yan, H.; Chang, G. L.; Li, Z.; Niu, M. J.; Hong, M. Organotin(IV) complexes derived from hydrazone Schiff base: synthesis, crystal structure, in vitro cytotoxicity and DNA/BSA interactions. Inorg. Chim. Acta 2017, 464, 137–146.
(32) Thomas, R. K.; Sukumaran, S.; Sudarsanakumar, C. Photobehaviour and in vitro binding strategy of natural drug, chlorogenic acid with DNA: a case of groove binding. J. Mol. Struct. 2019, 1178, 62–72.
(33) Li, P.; Niu, M. J.; Hong, M.; Cheng, S.; Dou, J. Effect of structure and composition of nickel(II) complexes with salicylidene Schiff base ligands on their DNA/protein interaction and cytotoxicity. J. Inorg. Biochem. 2014, 137, 101–108.
(34) Kniep, B.; Huenig, T. R.; Fitch, F. W.; Heuer, J.; Koelsch, E.; Meuhlradt, P. F. Neutral glycosphingolipids of murine myeloma cells and helper, cytolytic, and suppressor T lymphocytes. Biochem. 1983, 22, 251–255.
(35) Bi, S.; Zhou, H.; Wu, J.; Sun, X. Y. Micronomicin/tobramycin binding with DNA: fluorescence studies using of ethidium bromide as a probe and molecular docking analysis. J. Biomol. Struct. Dyn. 2018, 1–13.
(36) Husain, M. A.; Ishqi, H. M.; Sarwar, T.; Rehman, S. U.; Tabish, M. Interaction of indomethacin with calf thymus DNA: a multi-spectroscopic, thermodynamic and molecular modeling approach. Medchemcomm 2017, 8, 1283–1296.
(37) Gaur, R.; Khan, R. A.; Tabassum, S.; Shah, P.; Siddiqi, M. I.; Mishra, L. Interaction of a ruthenium(II)-chalcone complex with double stranded DNA: spectroscopic, molecular docking and nuclease properties. J. Photoch. Photobio. A 2011, 220, 145–152.
(38) Benyamini, H.; Shulmanpeleg, A.; Wolfson, H. J.; Belgorodsky, B.; Fadeev, L.; Gozin, M. Interaction of C60-fullerene and carboxyfullerene with proteins: docking and binding site alignment. Bioconjugate Chem. 2006, 17, 378–386.
(39) Wei, Q.; Dong, J.; Zhao, P.; Li, M.; Cheng, F.; Kong, J.; Li, L. DNA binding, BSA interaction and SOD activity of two new nickel(II) complexes with glutamine Schiff base ligands. J. Photoch. Photobio. B 2016, 161, 355–367.
(40) Sasmal, M.; Bhowmick, R.; Islam, A. S. M.; Bhuiya, S.; Das, S.; Ali, M. Domain-specific association of a phenanthrene-pyrene-based synthetic fluorescent probe with bovine serum albumin: spectroscopic and molecular docking analysis. ACS Omega 2018, 3, 6293–6304.
(41) Gensch, T.; Hendriks, J.; Hellingwerf, K. J. Tryptophan fluorescence monitors structural changes accompanying signaling state formation in the photocycle of photoactive yellow protein. Photochem. Photobiol. Sci. 2004, 3, 531–536.
(42) Klajnert, B.; Stanisławska, L.; Bryszewska, M.; Pałecz, B. Interactions between PAMAM dendrimers and bovine serum albumin. Biochim. Biophys. Acta 2003, 1648, 115–126.
(43) Zhang, Y. Z.; Zhou, B.; Liu, Y. X.; Zhou, C. X.; Ding, X. L.; Liu, Y. Fluorescence study on the interaction of bovine serum albumin with P-aminoazobenzene. J. Fluoresc. 2008, 18, 109–118.
(44) Sahoo, D.; Bhattacharya, P.; Chakravorti, S. Reverse micelle induced flipping of binding site and efficiency of albumin Protein with an ionic styryl dye. J. Phys. Chem. B 2010, 114, 10442–10450.
(45) Lu, Y. X.; Shi, T.; Wang, Y.; Yang, H. Y.; Yan, X. H.; Luo, X. M.; Jiang, H. L.; Zhu, W. L. Halogen bonding—a novel interaction for rational drug design? J. Med. Chem. 2009, 52, 2854–2862.