The Anticancer Activities of Some Nitrogen Donor Ligands Containing Bis-Pyrazole, Bipyridine, and Phenanthroline Moiety Using Docking Methods

Overview

Journal Bioinorg Chem Appl

Publisher Wiley

Date 2018 Jul 4

PMID 29967635

Citations 4

Authors

Adebayo A Adeniyi

Peter A Ajibade

Affiliations

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Abstract

The anticancer study of nitrogen-chelating ligands can be of tremendous help in choosing ligands for the anticancer metal complexes design especially with ruthenium(II). The inhibitory anticancer activities of some nitrogen-chelating ligands containing bis-pyrazole, bipyridine, and phenanthroline were studied using experimental screening against cancer cell and theoretical docking methods. anticancer activities showed compound as the most promising inhibitor, and the computational docking further indicates its strong inhibitory activities towards some cancer-related receptors. Among the twenty-one modelled ligands, pyrazole-based compounds , , and are the most promising inhibitors against the selected receptors followed by and which are derivatives of pyridine and phenanthroline, respectively. The presence of the carboxylic unit in the top five ligands that displayed stronger inhibitory activities against the selected receptors is an indication that the formation of noncovalent interactions such as hydrogen bonding and a strong electron-withdrawing group in these compounds are very important for their receptor interactions. The thermodynamic properties, the polarizabilities, and the LUMO energy of the compounds are in the same patterns as the observed inhibitory activities.

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References

World C, Yamawaki H, Berk B . Thioredoxin in the cardiovascular system. J Mol Med (Berl). 2006; 84(12):997-1003. DOI: 10.1007/s00109-006-0109-6. View

Fu Y, Habtemariam A, Basri A, Braddick D, Clarkson G, Sadler P . Structure-activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity. Dalton Trans. 2011; 40(40):10553-62. DOI: 10.1039/c1dt10937e. View

Castellano-Castillo M, Kostrhunova H, Marini V, Kasparkova J, Sadler P, Malinge J . Binding of mismatch repair protein MutS to mispaired DNA adducts of intercalating ruthenium(II) arene complexes. J Biol Inorg Chem. 2008; 13(6):993-9. DOI: 10.1007/s00775-008-0386-3. View

Kostrhunova H, Florian J, Novakova O, Peacock A, Sadler P, Brabec V . DNA interactions of monofunctional organometallic osmium(II) antitumor complexes in cell-free media. J Med Chem. 2008; 51(12):3635-43. DOI: 10.1021/jm701538w. View

Caballero N, Melendez F, Nino A, Munoz-Caro C . Molecular docking study of the binding of aminopyridines within the K+ channel. J Mol Model. 2007; 13(5):579-86. DOI: 10.1007/s00894-007-0184-9. View

Xie P, Streu C, Qin J, Bregman H, Pagano N, Meggers E . The crystal structure of BRAF in complex with an organoruthenium inhibitor reveals a mechanism for inhibition of an active form of BRAF kinase. Biochemistry. 2009; 48(23):5187-98. PMC: 2929178. DOI: 10.1021/bi802067u. View

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View

Hu W, Luo Q, Ma X, Wu K, Liu J, Chen Y . Arene control over thiolate to sulfinate oxidation in albumin by organometallic ruthenium anticancer complexes. Chemistry. 2009; 15(27):6586-94. DOI: 10.1002/chem.200900699. View

Holdgate G, Tunnicliffe A, WARD W, Weston S, Rosenbrock G, Barth P . The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study. Biochemistry. 1997; 36(32):9663-73. DOI: 10.1021/bi970294+. View

10.

Stepanenko I, Casini A, Edafe F, Novak M, Arion V, Dyson P . Conjugation of organoruthenium(II) 3-(1H-benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and indolo[3,2-d]benzazepines to recombinant human serum albumin: a strategy to enhance cytotoxicity in cancer cells. Inorg Chem. 2011; 50(24):12669-79. PMC: 3255472. DOI: 10.1021/ic201801e. View

11.

Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G . Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc Natl Acad Sci U S A. 2001; 98(17):9533-8. PMC: 55487. DOI: 10.1073/pnas.171178698. View

12.

Liu X, Chen Z, Li L, Chen Y, Lu J, Zhang D . DNA-binding, photocleavage studies of ruthenium(II) complexes with 2-(2-quinolinyl) imidazo[4,5-f][1,10]phenanthroline. Spectrochim Acta A Mol Biomol Spectrosc. 2012; 102:142-9. DOI: 10.1016/j.saa.2012.10.025. View

13.

Casini A, Gabbiani C, Sorrentino F, Rigobello M, Bindoli A, Geldbach T . Emerging protein targets for anticancer metallodrugs: inhibition of thioredoxin reductase and cathepsin B by antitumor ruthenium(II)-arene compounds. J Med Chem. 2008; 51(21):6773-81. DOI: 10.1021/jm8006678. View

14.

Xu L, Zhong N, Huang H, Liang Z, Li Z, Liu Y . Synthesis, characterization, cellular uptake, apoptosis, cytotoxicity, dna-binding, and antioxidant activity studies of ruthenium(II) complexes. Nucleosides Nucleotides Nucleic Acids. 2012; 31(8):575-91. DOI: 10.1080/15257770.2012.704110. View

15.

Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K . Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng. 1999; 12(6):439-46. DOI: 10.1093/protein/12.6.439. View

16.

Gu S, Liu B, Chen J, Wu H, Chen W . Synthesis, structures, and properties of ruthenium(II) complexes of N-(1,10-phenanthrolin-2-yl)imidazolylidenes. Dalton Trans. 2011; 41(3):962-70. DOI: 10.1039/c1dt11269d. View

17.

Newby Z, Lee T, Morse R, Liu Y, Liu L, Venkatraman P . The role of protein dynamics in thymidylate synthase catalysis: variants of conserved 2'-deoxyuridine 5'-monophosphate (dUMP)-binding Tyr-261. Biochemistry. 2006; 45(24):7415-28. PMC: 2556892. DOI: 10.1021/bi060152s. View

18.

Dougan S, Habtemariam A, McHale S, Parsons S, Sadler P . Catalytic organometallic anticancer complexes. Proc Natl Acad Sci U S A. 2008; 105(33):11628-33. PMC: 2503924. DOI: 10.1073/pnas.0800076105. View

19.

Adeniyi A, Ajibade P . Experimental and theoretical investigation of the spectroscopic and electronic properties of pyrazolyl ligands. Spectrochim Acta A Mol Biomol Spectrosc. 2014; 133:831-45. DOI: 10.1016/j.saa.2014.06.030. View

20.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View