Advertisement

Structural Chemistry

, Volume 30, Issue 6, pp 2225–2243 | Cite as

Structural correlation and computational quantum chemical explorations of two 1,2,3-triazolyl-methoxypyridine derivatives as CYP51 antifungal inhibitors

  • C. RavikumarEmail author
  • S. Murugavel
Original Research
  • 144 Downloads

Abstract

Structural correlation and computational quantum chemical optimization of two 1,2,3-triazolyl-methoxypyridine derivatives fused with a five-membered heterocyclic moiety, furan (I) or thiophene (II), were performed. Compounds I and II belong to the triclinic crystal classification with P-1 space group. The bond lengths and angles of the optimized crystal structures are in good agreement with the XRD experimental data. We confirmed the hydrogen bonding interactions that observed in crystal packing of compounds I and II using Hirshfeld surface and energy framework analysis. The DFT functional non-linear optical and thermochemistry parameters of the title compounds were calculated. The local reactivity domains of compounds I and II were recognized by the Fukui function parameter analysis. In silico molecular docking simulations were carried out to discover the lanosterol 14 α-demethylase (CYP51) enzyme inhibition against target protein (PDB ID: 1EA1). Antifungal activity of the title molecules was predicted by in vitro antifungal studies against three fungal strains using fungal drug fluconazole as a positive control. Compound I exhibited enhanced affinity with receptor 1EA1 and higher inhibition activity with fungal strains compared to compound II.

Keywords

1,2,3-triazole Hirshfeld surface Fukui function NLO In silico docking CYP51 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG, White TC (2012) Hidden killers: human fungal infections. Sci Transl Med 4:1–9.  https://doi.org/10.1126/scitranslmed.3004404 CrossRefGoogle Scholar
  2. 2.
    Bongomin F, Gago S, Oladele R, Denning D (2017) Global and multi-national prevalence of fungal diseases—estimate precision. J Fungi 3(4):57.  https://doi.org/10.3390/jof3040057 CrossRefGoogle Scholar
  3. 3.
    Armstrong-James D, Meintjes G, Brown GD (2014) A neglected epidemic: fungal infections in HIV/AIDS. Trends Microbiol 22:120–127.  https://doi.org/10.1016/j.tim.2014.01.001 CrossRefPubMedGoogle Scholar
  4. 4.
    Ji H, Zhang W, Zhou Y, Zhang M, Zhu J, Song Y, Lü J, Zhu J (2000) A three-dimensional model of lanosterol 14α-demethylase of Candida albicans and its interaction with azole antifungals. J Med Chem 43(13):2493–2505PubMedGoogle Scholar
  5. 5.
    Gollapudy R, Ajmani S, Kulkarni SA (2004) Modeling and interactions of Aspergillus fumigatus lanosterol 14-α demethylase ‘A’ with azole antifungals. Bioorg Med Chem 12(11):2937–2950PubMedGoogle Scholar
  6. 6.
    Nikalje AP, Tiwari SV, Sarkate AP, Karnik KS (2018) Imidazole-thiazole coupled derivatives as novel lanosterol 14-α demethylase inhibitors: ionic liquid mediated synthesis, biological evaluation and molecular docking study. Med Chem Res 27(2):592–606Google Scholar
  7. 7.
    Garcia-Rubio R, Monteiro MC, & Mellado E (2018). Azole antifungal drugs: mode of action and resistance. Reference Module in Life Sci, Elsevier  https://doi.org/10.1016/b978-0-12-809633-8.20731-0 Google Scholar
  8. 8.
    Helda Malarkodi J, Murugavel S, Rosaline Ezhilarasi J, Dinesh M, Ponnuswamy A (2018) A structure investigation, spectral characterization, electronic properties, and antimicrobial and molecular docking studies of 3′-(1-benzyl-5-methyl-1H-1,2,3-triazole-4-carbonyl)-1′-methyl-4′-phenyl-2H-spiro [acenaphthylene-1,2′-pyrrolidine]-2-one. J Chin Chem Soc 2019;66:205– 217  https://doi.org/10.1002/jccs.201800128 Google Scholar
  9. 9.
    Dheer D, Singh V, Shankar R (2017) Medicinal attributes of 1,2,3-triazoles: current developments. Bioorg Chem 71:30–54PubMedGoogle Scholar
  10. 10.
    Khan MR, Soni LK, Nema RK, Balekar N (2017) Designing of new benzotriazole analogs using molecular docking studies against receptor 1EA1. Pdb & 1IYL. Pdb for treatment of fungal infection. J Drug Deliv Ther 7(7):139–141Google Scholar
  11. 11.
    Lei J, Xu J, Wang T (2018) In vitro susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole and the correlation between triazoles susceptibility: results from a five-year study. J Mycol Med 28(2):310–313PubMedGoogle Scholar
  12. 12.
    Murugavel S, Ravikumar C, Jaabil G, Alagusundaram P (2019) Synthesis, crystal structure analysis, spectral investigations (NMR, FT-IR, UV), DFT calculations, ADMET studies, molecular docking and anticancer activity of 2-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2-chlorophenyl)-6-methoxypyridine–a novel potent human topoisomerase IIα inhibitor. J Mol Struct 1176:729–742Google Scholar
  13. 13.
    Ma LY, Pang LP, Wang B, Zhang M, Hu B, Xue DQ, Shao KP, Zhang BL, Liu Y, Zhang E et al (2014) Design and synthesis of novel 1,2,3-triazole-pyrimidine hybrids as potential anticancer agents. Eur J Med Chem 86:368–380PubMedGoogle Scholar
  14. 14.
    Tan W, Li Q, Li W, Dong F, Guo Z (2016) Synthesis and antioxidant property of novel 1,2,3-triazole-linked starch derivatives via “click chemistry”. Int J Biol Macromol 82:404–410PubMedGoogle Scholar
  15. 15.
    Sumangala V, Poojary B, Chidananda N, Fernandes J, Kumari NS (2010) Synthesis and antimicrobial activity of 1,2,3-triazoles containing quinoline moiety. Arch Pharm Res 33:1911–1918PubMedGoogle Scholar
  16. 16.
    Kant R, Kumar D, Agarwal D, Gupta RD, Tilak R, Awasthi SK, Agarwal A (2016) Synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities. Eur J Med Chem 113:34–49PubMedGoogle Scholar
  17. 17.
    Altimari JM, Hockey SC, Boshoff HI, Sajid A, Henderson LC (2015) Novel 1,4-substituted-1,2,3-triazoles as antitubercular agents. ChemMedChem 10:787–791PubMedGoogle Scholar
  18. 18.
    Wu G, Gao Y, Kang D, Huang B, Huo Z, Liu H, Poongavanam V, Zhan P, Liu X (2018) Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives as potent cholinesterase inhibitors. MedChemComm. 9(1):149–159PubMedGoogle Scholar
  19. 19.
    Akın Ş, Demir EA, Colak A, Kolcuoglu Y, Yildirim N, Bekircan O (2019) Synthesis, biological activities and molecular docking studies of some novel 2,4,5-trisubstituted-1,2,4-triazole-3-one derivatives as potent tyrosinase inhibitors. J Mol Struct 1175:280–286Google Scholar
  20. 20.
    Lu K, Cai L, Zhang X, Wu G, Xu C, Zhao Y, Gong P (2018) Design, synthesis, and biological evaluation of novel substituted benzamide derivatives bearing a 1,2,3-triazole moiety as potent human dihydroorotate dehydrogenase inhibitors. Bioorg Chem 76:528–537PubMedGoogle Scholar
  21. 21.
    Vatmurge NS, Hazra BG, Pore VS, Shirazi F, Chavan PS, Dehpande MV (2008) Synthesis and antimicrobial activity of β-lactam-bile acid conjugates linked via triazole. Bioorg Med Chem Lett 18:2043–2047PubMedGoogle Scholar
  22. 22.
    Jagasia R, Holub JM, Bollinger M, Kirshenbaum K, Finn MG (2009) Peptide cyclization and cyclodimerization by CuI-mediated azide−alkyne cycloaddition. J Organomet Chem 74:2964–2974Google Scholar
  23. 23.
    Huber D, Hübner H, Gmeiner P (2009) 1,1′-Disubstituted ferrocenes as molecular hinges in mono- and bivalent dopamine receptor ligands. J Med Chem 52:6860–6870PubMedGoogle Scholar
  24. 24.
    Lamb DC, Kelly DE, Waterman MR, Stromstedt M, Rozman D, Kelly SL (1999) Characteristics of the heterologously expressed human lanosterol 14α-demethylase (other names: P45014DM, CYP51, P45051) and inhibition of the purified human and Candida albicans CYP51 with azole antifungal agents. Yeast. 15(9):755–763PubMedGoogle Scholar
  25. 25.
    Sanati H, Belanger P, Fratti R, Ghannoum M (1997) A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. Antimicrob Agents Chemother 41(11):2492–2496PubMedPubMedCentralGoogle Scholar
  26. 26.
    Warrilow AG, Parker JE, Kelly DE, Kelly SL (2013) Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens. Antimicrob Agents Chemother 57:1352–1360PubMedPubMedCentralGoogle Scholar
  27. 27.
    Shanmugavelan P, Sathishkumar M, Nagarajan S, Ponnuswamy A (2012) A facile synthesis of 1,2,3-triazolyl indole hybrids via SbCl 3-catalysed Michael addition of indoles to 1,2,3-triazolyl chalcones. J Chem Sci 124(4):941–950Google Scholar
  28. 28.
    Jaabil G, Ranganathan R, Ponnuswamy A, Suresh P, Shanmugaiah V, Ravikumar C, Murugavel S (2018) A green and efficient synthesis of bioactive 1,2,3-triazolyl-pyridine/cyanopyridine hybrids via one-pot multicomponent grinding protocol. ChemistrySelect. 3(37):10388–10393Google Scholar
  29. 29.
    Hehre WJ, Ditchfield R, Pople JA (1972) Self—consistent molecular orbital methods. XII. Further extensions of Gaussian—type basis sets for use in molecular orbital studies of organic molecules. J Chem Phys 56(5):2257–2261Google Scholar
  30. 30.
    Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Accounts 120(1–3):215–241Google Scholar
  31. 31.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, & Nakatsuji, H (2009) Gaussian 09, revision D. 01. Gaussian Inc Wallingford, CT.Google Scholar
  32. 32.
    Dennington R, Keith T, Millam J (2009) GaussView, version 5. Semichem Inc., Shawnee MissionGoogle Scholar
  33. 33.
    Wolff SK, Grimwood DJ, McKinnon JJ, Turner MJ, Jayatilaka D, Spackman MA (2012) Crystal explorer (Version 3.1). University of Western AustraliaGoogle Scholar
  34. 34.
    Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98(7):5648–5652Google Scholar
  35. 35.
    Morell C, Grand A, Toro-Labbe A (2005) New dual descriptor for chemical reactivity. J Phys Chem A 109(1):205–212PubMedGoogle Scholar
  36. 36.
    Pearson RG (1992) The electronic chemical potential and chemical hardness. J Mol Struct THEOCHEM 255:261–270Google Scholar
  37. 37.
    RCSB PDB www.rcsb.org. Accessed on 20 Feb 2019
  38. 38.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242PubMedPubMedCentralGoogle Scholar
  39. 39.
    Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 2009(16):2785–2791Google Scholar
  40. 40.
    Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31:455–461PubMedPubMedCentralGoogle Scholar
  41. 41.
    Discovery Studio (2015) Dassault Systemes BIOVIA, Discovery Studio Modelling Environment, Release 4.5. Dassault Systemes, San DiegoGoogle Scholar
  42. 42.
    Murugavel S, Sundramoorthy S, Subashini R, Pavan P (2018) Synthesis, characterization, pharmacological, molecular modeling and antimicrobial activity evaluation of novel isomer quinoline derivatives. Struct Chem 29(6):1677–1695Google Scholar
  43. 43.
    Mu JX, Shi YX, Wu HK, Sun ZH, Yang MY, Liu XH, Li BJ (2016) Microwave assisted synthesis, antifungal activity, DFT and SAR study of 1,2,4-triazolo [4,3-a] pyridine derivatives containing hydrazone moieties. Chem Central J 10(1):50Google Scholar
  44. 44.
    Lü R, Qu Z, Lin J (2013) Comparative study of interactions between thiophene\pyridine\benzene\heptane and 1-butyl-3-methylimidazolium trifluoromethanesulfonate by density functional theory. J Mol Liq 180:207–214Google Scholar
  45. 45.
    Tyagi P, Chandra S, Saraswat BS, Yadav D (2015) Design, spectral characterization, thermal, DFT studies and anticancer cell line activities of Co (II), Ni (II) and Cu (II) complexes of Schiff bases derived from 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol. Spectrochim Acta A Mol Biomol Spectrosc 145:155–164PubMedGoogle Scholar
  46. 46.
    Sharma YR (2010) Elementary organic spectroscopy, Principles and chemical applications. S Chand & Co. Ltd, New DelhiGoogle Scholar
  47. 47.
    Mohan J (2004) Organic spectroscopy: principles amp; applications. Harrow U.K., Alpha Science International LtdGoogle Scholar
  48. 48.
    Colthup NB (1950) Spectra-structure correlations in the infra-red region. J Opt Soc of Am [Internet]. The Optical Society 40(6):397.  https://doi.org/10.1364/josa.40.000397 CrossRefGoogle Scholar
  49. 49.
    Puviarasan N, Arjunan V, Mohan S (2004) FTIR and FT-Raman spectral investigations on 4-aminoquinaldine and 5-aminoquinoline. Turk J Chem 28(1):53–66Google Scholar
  50. 50.
    Pang R, Hu X, Zhou S, Sun C, Yan J, Sun X, Xiao S, Chen P (2014) Preparation of multi-shelled conductive polymer hollow microspheres by using Fe 3 O 4 hollow spheres as sacrificial templates. Chem Commun 50(83):12493–12496Google Scholar
  51. 51.
    Rohl AL, Moret M, Kaminsky W, Claborn K, McKinnon JJ, Kahr B (2008) Hirshfeld surfaces identify inadequacies in computations of intermolecular interactions in crystals: pentamorphic 1,8-dihydroxyanthraquinone. Cryst Growth Des 8(12):4517–4525Google Scholar
  52. 52.
  53. 53.
  54. 54.
  55. 55.
    Kumar S, Kumar B (2018) Growth of an 8-hydroxyquinoline single crystal by a modified Czochralski growth technique, and crystal characterization. CrystEngComm. 20(5):624–630Google Scholar
  56. 56.
    Turner MJ, Thomas SP, Shi MW, Jayatilaka D, Spackman MA (2015) Energy frameworks: insights into interaction anisotropy and the mechanical properties of molecular crystals. Chemical communications. R Soc Chem (RSC) 51(18):3735–3738.  https://doi.org/10.1039/c4cc09074h CrossRefGoogle Scholar
  57. 57.
    Mackenzie CF, Spackman PR, Jayatilaka D, Spackman MA (2017) CrystalExplorer model energies and energy frameworks: extension to metal coordination compounds, organic salts, solvates and open-shell systems. IUCrJ. 4(5):575–587PubMedPubMedCentralGoogle Scholar
  58. 58.
    Suresh S, Ramanand A, Jayaraman D, Mani P (2012) Review on theoretical aspect of nonlinear optics. Rev Adv Mater Sci 30:175–183Google Scholar
  59. 59.
    Shakir M, Kushwaha SK, Maurya KK, Arora M, Bhagavannarayana G (2009) Growth and characterization of glycine picrate—remarkable second-harmonic generation in centrosymmetric crystal. J Cryst Growth 311(15):3871–3875Google Scholar
  60. 60.
    Nalla V, Medishetty R, Wang Y, Bai Z, Sun H, Wei J, Vittal JJ (2015) Second harmonic generation from the centrosymmetric crystals. IUCrJ. 2(3):317–321PubMedPubMedCentralGoogle Scholar
  61. 61.
    Amudha M, Rajkumar R, Thayanithi V, Praveen KP (2015) Growth and characterization of benzimidazolium salicylate: NLO property from a centrosymmetric crystal. Adv Opt Technol Hindawi limited 2015:1–9.  https://doi.org/10.1155/2015/206325 CrossRefGoogle Scholar
  62. 62.
    Suponitsky KY, Tafur S, Masunov AE (2008) Applicability of hybrid density functional theory methods to calculation of molecular hyperpolarizability. J Chem Phys 129(4):044109PubMedGoogle Scholar
  63. 63.
    Reis H, Papadopoulos MG, Munn RW (1998) Calculation of macroscopic first-, second-, and third-order optical susceptibilities for the urea crystal. J Chem Phys 109(16):6828–6838Google Scholar
  64. 64.
    Beena T, Sudha L, Nataraj A, Balachandran V, Kannan D, Ponnuswamy MN (2017) Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2 H-chromen-2-one: an anticancer agent. Chem Central J 11(1):6Google Scholar
  65. 65.
  66. 66.
    FR B, Prasana JC, Muthu S, Abraham CS (2019) Molecular docking studies, charge transfer excitation and wave function analyses (ESP, ELF, LOL) on valacyclovir: a potential antiviral drug. Comput Biol Chem [Internet] Elsevier BV 78:9–17.  https://doi.org/10.1016/j.compbiolchem.2018.11.014 CrossRefGoogle Scholar
  67. 67.
    Li Y, Evans JN (1995) The Fukui function: a key concept linking frontier molecular orbital theory and the hard-soft-acid-base principle. J Am Chem Soc 117(29):7756–7759Google Scholar
  68. 68.
    Frau J, Glossman-Mitnik D (2017) A conceptual DFT study of the molecular properties of glycating carbonyl compounds. Chem Central J 11(1):8Google Scholar
  69. 69.
    Pearson RG (1989) Absolute electronegativity and hardness: applications to organic chemistry. J Organic Chem 54(6):1423–1430Google Scholar
  70. 70.
    Zhou Z, Parr RG (1990) Activation hardness: new index for describing the orientation of electrophilic aromatic substitution. J Am Chem Soc 112(15):5720–5724Google Scholar
  71. 71.
    Ghosh DC, Jana J (1999) A study of correlation of the order of chemical reactivity of a sequence of binary compounds of nitrogen and oxygen in terms of frontier orbital theory. Curr Sci 25:570–573Google Scholar
  72. 72.
    Domingo LR, Aurell MJ, Pérez P, Contreras R (2002) Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels-Alder reactions. Tetrahedron 58:4417–4423Google Scholar
  73. 73.
    Makov G (1995) Chemical hardness in density functional theory. J Phys Chem 99(23):9337–9339Google Scholar
  74. 74.
    Pearson RG (2005) Chemical hardness and density functional theory. J Chem Sci 117(5):369–377Google Scholar
  75. 75.
    Katsila T, Spyroulias GA, Patrinos GP, Matsoukas MT (2016) Computational approaches in target identification and drug discovery. Comput Struct Biotechnol J 14:177–184PubMedPubMedCentralGoogle Scholar
  76. 76.
    Podust LM, Poulos TL, Waterman MR (2001) Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from mycobacterium tuberculosis in complex with azole inhibitors. Proc Natl Acad Sci 98(6):3068–3073PubMedGoogle Scholar
  77. 77.
    Mohapatra RK, Sarangi AK, Azam M, El-ajaily MM, Kudrat-E-Zahan M, Patjoshi SB, Dash DC (2019) Synthesis, structural investigations, DFT, molecular docking and antifungal studies of transition metal complexes with benzothiazole based Schiff base ligands. J Mol Struct 1179:65–75Google Scholar
  78. 78.
    Sahu JK, Ganguly S, Yasir M (2018) Synthesis, SAR and molecular docking studies of certain new derivatives of 1,2,4-triazolo [3,4-b][1,3,4] thiadiazole as potent antimicrobial agents. Anti-Infect Agents 16(1):40–48Google Scholar
  79. 79.
    Biemer JJ (1973) Antimicrobial susceptibility testing by the Kirby-Bauer disc diffusion method. Ann Clin Lab Sci 3(2):135–140PubMedGoogle Scholar
  80. 80.
    Maldonado J, Ghemri H, Vanelle P, Crozet M, Timon-David P, Julien JM, Gasquet M, Augier J (1987) Furan and thiophene derivatives with antifungal properties. ChemInform. 18(20) https://doi.org/10.1002/chin.198720179
  81. 81.
    Sheng C, Zhang W (2011) New lead structures in antifungal drug discovery. Curr Med Chem 18(5):733–766PubMedGoogle Scholar
  82. 82.
    Peng XM, Cai GX, Zhou CH (2013) Recent developments in azole compounds as antibacterial and antifungal agents. Curr Top Med Chem 13(16):1963–2010PubMedGoogle Scholar
  83. 83.
    Faghih-Mirzaei E, Seifi M, Abaszadeh M, Zomorodian K, Helali H (2018) Design, synthesis, biological evaluation and molecular modeling study of novel indolizine-1-carbonitrile derivatives as potential anti-microbial agents. Iran J Pharm Res: IJPR 17(3):883PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PhysicsThanthai Periyar EVR Government Polytechnic CollegeVelloreIndia
  2. 2.Department of PhysicsThanthai Periyar Government Institute of TechnologyVelloreIndia

Personalised recommendations