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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

Author(s): Claudiu N. Lungu*, Bogdan Ionel Bratanovici , Maria Mirabela Grigore, Vasilichia Antoci and Ionel I. Mangalagiu*

Volume 27, Issue 1, 2020

Page: [154 - 169] Pages: 16

DOI: 10.2174/0929867326666181220094229

Price: $65

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Abstract

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Keywords: Anticancer drugs, DNA intercalators, docking, binding site, hybrid imidazole-pyridine derivatives, QSAR model.

[1]
Richaud, A.; Barba-Behrens, N.; Méndez, F. Chemical reactivity of the imidazole: a semblance of pyridine and pyrrole? Org. Lett., 2011, 13(5), 972-975.
[http://dx.doi.org/10.1021/ol103011h] [PMID: 21268606]
[2]
Zhang, L.; Peng, X.M.; Damu, G.L.; Geng, R.X.; Zhou, C.H. Comprehensive review in current developments of imidazole-based medicinal chemistry. Med. Res. Rev., 2014, 34(2), 340-437.
[http://dx.doi.org/10.1002/med.21290] [PMID: 23740514]
[3]
Neidle, S.; Pearl, L.H.; Herzyk, P.; Berman, H.M. A molecular model for proflavine-DNA intercalation. Nucleic Acids Res., 1988, 16(18), 8999-9016.
[http://dx.doi.org/10.1093/nar/16.18.8999] [PMID: 3174439]
[4]
Richards, A.D.; Rodger, A. Synthetic metallomolecules as agents for the control of DNA structure. Chem. Soc. Rev., 2007, 36(3), 471-483.
[http://dx.doi.org/10.1039/B609495C] [PMID: 17325786]
[5]
Luzzati, V.; Masson, F.; Lerman, L.S. Interaction of DNA and proflavine: a small-angle x-ray scattering study. J. Mol. Biol., 1961, 3(5), 634-639.
[http://dx.doi.org/10.1016/S0022-2836(61)80026-0] [PMID: 14467543]
[6]
Gai, D.; Chang, Y.P.; Chen, X.S. Origin DNA melting and unwinding in DNA replication. Curr. Opin. Struct. Biol., 2010, 20(6), 756-762.
[http://dx.doi.org/10.1016/j.sbi.2010.08.009] [PMID: 20870402]
[7]
Morávek, Z.; Neidle, S.; Schneider, B. Protein and drug interactions in the minor groove of DNA. Nucleic Acids Res., 2002, 30(5), 1182-1191.
[http://dx.doi.org/10.1093/nar/30.5.1182] [PMID: 11861910]
[8]
Hall, D.R.; Kozakov, D.; Whitty, A.; Vajda, S. Lessons from hot spot analysis for fragment-based drug discovery. Trends Pharmacol. Sci., 2015, 36(11), 724-736.
[http://dx.doi.org/10.1016/j.tips.2015.08.003] [PMID: 26538314]
[9]
Dorina, M.; Vasilichia, A.; Costel, M.; Gheorghita, Z. Ionel, I., Mangalagiu. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity. J. Enzyme Inhib. Med. Chem., 2016, 31(2), 96-103.
[http://dx.doi.org/10.1080/14756366.2016.1190711] [PMID: 27250919]
[10]
Shoemaker, R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer, 2006, 6(10), 813-823.
[http://dx.doi.org/10.1038/nrc1951] [PMID: 16990858]
[11]
National Cancer Instituite. Developmental Therapeutics Program, Available at:. http://dtp.nci.nih.gov/docs/compare/compare.html November 17, 2017
[12]
Tereshko, V.; Minasov, G.; Egli, M. The Dickerson-Drew B-DNADodecamer Revisited-AtAtomic Resolution. J. Am. Chem. Soc., 1999, 121(2), 470-471.
[http://dx.doi.org/10.1021/ja9832919]
[13]
Dai, J.; Chen, D.; Jones, R.A.; Hurley, L.H.; Yang, D. NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nucleic Acids Res., 2006, 34(18), 5133-5144.
[http://dx.doi.org/10.1093/nar/gkl610] [PMID: 16998187]
[14]
Yi, C.; He, C. DNA repair by reversal of DNA damage. Cold Spring Harb. Perspect. Biol., 2013, 5(1) a012575
[http://dx.doi.org/10.1101/cshperspect.a012575] [PMID: 23284047]
[15]
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[http://dx.doi.org/ 10.1002/jcc.21334] [PMID: 19499576]
[16]
Mihai, V. Putz, Nicoleta A. Dudaṣ. Variational principles for mechanistic quantitative structure-activity relationship (QSAR) studies: application on uracil derivates’ anti HIV action. Struct. Chem., 2013, 24(6), 1873-1893.
[http://dx.doi.org/10.1007/s11224-013-0249-6]
[17]
Putz, M.V.; Dudaş, N.A. Determining chemical reactivity driving biological activity from SMILES transformations: the bonding mechanism of anti-HIV pyrimidines. Molecules, 2013, 18(8), 9061-9116.
[http://dx.doi.org/10.3390/molecules18089061] [PMID: 23903183]

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