Molecular docking studies on binding specificity of 3,6- and 2,7-carbazoles with DNA duplexes

  • Anwesh Pandey Department of Physics, Babasaheb Bhimrao Ambedkar University, Lucknow-226025, U.P., India
  • Manas Misra Department of Physics, Babasaheb Bhimrao Ambedkar University, Lucknow-226025, U.P., India
  • Anil Kumar Yadav Department of Physics, Babasaheb Bhimrao Ambedkar University, Lucknow-226025, U.P., India
Keywords: Carbazoles, Docking, DNA, Minor Groove

Abstract

Molecular docking is a widely used computational technique used to find the probabilistic binding sites of drugs in the vicinity of macromolecules. The drugs produce their working effect only when they bind and interact with the target macromolecule. The potential drugs can only be identified by their relative binding affinities and corresponding binding modes. Availability of huge numbers of such drugs has made the estimation of their relative potency, a difficult task. In the present work, carbazoles (3,6 and 2,7) and their analogs were studied for their DNA binding abilities using molecular docking calculations. Since the docked ligands had planar structures, it allowed them to adopt crescent shape and thus minor groove binding with DNA was preferred by all. However, it was found that a single molecule (Mol-6) (2,7-carbazole) showed promising results with all the selected DNA sequences also its results were exactly verified with those in the reported literature and therefore it can be said that its in-vivo studies could possibly produce some exciting results. This study also revealed that DNA binding energies of 3,6- and 2,7-carbazoles followed the same trend as their thermal melting values.

DOI: http://dx.doi.org/10.5281/zenodo.4153709

Downloads

Download data is not yet available.

References

1. Watson JD, Crick FHC. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature. 1953; 171(4356): 737-738.

2. Mishra R, Singh Gaur A, Chandra R, Kumar D. Molecular docking and molecular dynamics study of DNA minor groove binders. Int J Pharm Chem Anal. 2015; 2(4): 161-169.

3. Pandey A, Mishra R, Yadav A. Understanding interactions of DNA minor groove binders using advanced computational techniques. Int J Anal Exp Modal Anal. 2020; 12: 1300-1315.

4. Dervan PB. Molecular recognition of DNA by small molecules. Bioorg Med Chem. 2001; 9(9): 2215-2235.

5. Pandey A, Mishra R, Shukla A, Yadav A, Kumar D. In-silico docking studies of 2,5-bis(4-amidinophenyl) furan and its derivatives. Proceeding of ISAFBM. 2019.

6. Shukla A, Mishra R, Pandey A, Dwivedi AK, Kumar D. Interaction of flavonols with DNA: molecular docking studies. Proceeding of ISAFBM. 2019.

7. Pandey A, Yadav R, Shukla A, Yadav AK. Unveiling the antimicrobial activities of dicationic carbazoles and related analogs through computational docking. Adv Sci Eng Med. 2020; 12(1): 40-44.

8. Yadav R, Pandey A, Awasthi N, Shukla A. Molecular docking studies of enzyme binding drugs on family of cytochrome P450. Adv Sci Eng Med. 2020; 12(1): 83-87.

9. Srivastava HK, Chourasia M, Kumar D, Sastry GN. Comparison of computational methods to model DNA minor groove binders. J Chem Inf Model. 2011; 51(3): 558-571.

10. Kamal A, Shetti RV, Ramaiah MJ, Swapna P, Reddy KS, Mallareddy A, et al. Carbazole-pyrrolo [2,1-c][1,4] benzodiazepine conjugates: design, synthesis, and biological evaluation. Medchemcomm. 2011; 2(8): 780-788.

11. Kamal A, Shankaraiah N, Reddy CR, Prabhakar S, Markandeya N, Srivastava HK, et al. Synthesis of bis-1,2,3-triazolo-bridged unsymmetrical pyrrolobenzodiazepine trimers via ‘click’chemistry and their DNA-binding studies. Tetrahedron. 2010; 66(29): 5498-5506.

12. Kamal A, Bharathi EV, Ramaiah MJ, Dastagiri D, Reddy JS, Viswanath A, et al. Quinazolinone linked pyrrolo [2,1-c][1,4] benzodiazepine (PBD) conjugates: design, synthesis and biological evaluation as potential anticancer agents. Bioorg Med Chem. 2010; 18(2): 526-542.

13. Kamal A, Reddy DR, Reddy MK, Balakishan G, Shaik TB, Chourasia M, et al. Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo [2,1-c][1,4] benzodiazepines and their anticancer potential. Bioorg Med Chem. 2009; 17(4): 1557-1572.

14. Kamal A, Khan MNA, Reddy KS, Rohini K, Sastry GN, Sateesh B, et al. Synthesis, structure analysis, and antibacterial activity of some novel 10-substituted 2-(4-piperidyl/phenyl)-5, 5-dioxo [1,2,4] triazolo [1,5-b][1,2,4] benzothiadiazine derivatives. Bioorg Med Chem Lett. 2007; 17(19): 5400-5405.

15. Tidwell RR, Boykin DW. Dicationic DNA minor groove binders as antimicrobial agents. Small Mol DNA RNA Bind Synth Nucleic Acid Complexes. 2002: 414-460.

16. Mishra R, Kumar A, Chandra R, Kumar D. A review on theoretical studies of various types of drug-DNA interaction. Int J Sci Technol Soc. 2017; 3: 11-27.

17. Drew HR, Wing RM, Takano T, Broka C, Tanaka S, Itakura K, et al. Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci. 1981; 78(4): 2179-2183.

18. Coll M, Aymami J, Van der Marel GA, Van Boom JH, Rich A, Wang AHJ. Molecular structure of the netropsin-d (CGCGATATCGCG) complex: DNA conformation in an alternating AT segment. Biochemistry. 1989; 28(1): 310-320.

19. Gavathiotis E, Sharman GJ, Searle MS. Sequence-dependent variation in DNA minor groove width dictates orientational preference of Hoechst 33258 in a-tract recognition: solution NMR structure of the 2: 1 complex with d (CTTTTGCAAAAG) 2. Nucleic Acids Res. 2000; 28(3): 728-735.

20. Anthony NG, Johnston BF, Khalaf AI, MacKay SP, Parkinson JA, Suckling CJ, et al. Short lexitropsin that recognizes the DNA minor groove at 5‘-ACTAGT-3‘: understanding the role of isopropyl-thiazole. J Am Chem Soc. 2004; 126(36): 11338-11349.

21. Balendiran K, Rao ST, Sekharudu CY, Zon G, Sundaralingam M. X-ray structures of the B-DNA dodecamer d(CGCGTTAACGCG) with an inverted central tetranucleotide and its netropsin complex. Acta Crystallogr Sect D. 1995; 51(2): 190-198.

22. Alniss HY, Salvia MV, Sadikov M, Golovchenko I, Anthony NG, Khalaf AI, et al. Recognition of the DNA minor groove by thiazotropsin analogues. ChemBioChem. 2014; 15(13): 1978-1990.

23. RCSB PDB - 4AH0: crystal structure of the DB 985-D(CGCAAATTTGCG)2 complex at 1.20 A resolution. n.d.

24. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The Protein Data Bank. Nucleic Acids Res. 2000; 28(1): 235-242.

25. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13): 1605-1612.

26. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 9, Revision B.01. Gaussian, Inc., Wallingford CT 2009.

27. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16): 2785-2791.

28. Baraldi PG, Cacciari B, Guiotto A, Romagnoli R, Zaid AN, Spalluto G. DNA minor-groove binders: results and design of new antitumor agents. Farm. 1999; 54(1-2): 15-25.

29. Blaney JM, Dixon JS. A Good ligand is hard to find: automated docking methods. Perspect Drug Discov Des. 1993; 1(2): 301-319.

30. Yadava U. Search algorithms and scoring methods in protein-ligand docking. Endocrinol Int J. 2018; 6(6): 359-367.

31. Chaires JB. Drug-DNA Interactions. Curr Opin Struct Biol. 1998; 314(320): 8.

32. Chalikian TV, Breslauer KJ. Thermodynamic analysis of biomolecules: a volumetric approach. Curr Opin Struct Biol. 1998; 8(5): 657-664.

33. Gilbert DE, Feigon J. Structural analysis of drug-DNA interactions. Curr Opin Struct Biol. 1991; 1(3): 439-445.

34. Shastri R, Awasthi N, Kumar D, Yadav AK, Roy D, Goutam SP, et al. A density functional theory study on structural stability and electronic properties of Co x O y (X+ Y= 4–12) nanoclusters. Adv Sci Eng Med. 2018; 10(7-8): 814-818.

35. Dassault Systèmes BIOVIA, Discovery Studio Visualizer. San Diego, Dassault Systèmes 2020.

36. Aamir M, Singh VK, Dubey MK, Meena M, Kashyap SP, Katari SK, et al. In silico prediction, characterization, molecular docking, and dynamic studies on fungal SDRs as novel targets for searching potential fungicides against Fusarium wilt in tomato. Front Pharmacol. 2018; 9: 1038.
Published
2020-10-29
How to Cite
(1)
Pandey, A.; Misra, M.; Yadav, A. Molecular Docking Studies on Binding Specificity of 3,6- and 2,7-Carbazoles With DNA Duplexes. European Journal of Biological Research 2020, 11, 14-23.
Section
Research Articles