Evaluation of Chemotherapeutic Activity of the Selected Bases’ Analogues of Nucleic Acids Supported by ab initio Various Quantum Chemical Calculations

Author(s): Piotr Kawczak*, Leszek Bober, Tomasz Bączek.

Journal Name: Current Computer-Aided Drug Design

Volume 16 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Pharmacological and physicochemical classification of bases’ selected analogues of nucleic acids is proposed in the study.

Objective: Structural parameters received by the PCM (Polarizable Continuum Model) with several types of calculation methods for the structures in vacuo and in the aquatic environment together with the huge set of extra molecular descriptors obtained by the professional software and literature values of biological activity were used to search the relationships.

Methods: Principal Component Analysis (PCA) together with Factor Analysis (FA) and Multiple Linear Regressions (MLR) as the types of the chemometric approach based on semi-empirical ab initio molecular modeling studies were performed.

Results: The equations with statistically significant descriptors were proposed to demonstrate both the common and differentiating characteristics of the bases' analogues of nucleic acids based on the quantum chemical calculations and biological activity data.

Conclusion: The obtained QSAR models can be used for predicting and explaining the activity of studied molecules.

Keywords: Nucleic acids analogues, chemotherapeutic activity, molecular modeling, descriptors, QSAR, PCA, FA, MLR.

[1]
Dinesh, S.; Shikha, G.; Bhavana, G.; Nidhi, S.; Dileep, S. Biological activities of purine analogues; a review. J. Pharm. Sci. Innov, 2012, 1, 29-34.
[2]
Sharma, V.; Chitranshi, N.; Agarwal, A.K. Significance and biological importance of pyrimidine in the microbial world. Int. J. Med. Chem., 2014, 2014202784
[http://dx.doi.org/10.1155/2014/202784] [PMID: 25383216 ]
[3]
Konc, J.; Lešnik, S.; Janežič, D. Modeling enzyme-ligand binding in drug discovery. J. Cheminform., 2015, 7(1), 48.
[http://dx.doi.org/10.1186/s13321-015-0096-0] [PMID: 26457119 ]
[4]
Štular, T.; Lešnik, S.; Rožman, K.; Schink, J.; Zdouc, M.; Ghysels, A.; Liu, F.; Aldrich, C.C.; Haupt, V.J.; Salentin, S.; Daminelli, S.; Schroeder, M.; Langer, T.; Gobec, S.; Janežič, D.; Konc, J. Discovery of Mycobacterium tuberculosis InhA inhibitors by binding sites comparison and ligands prediction. J. Med. Chem., 2016, 59(24), 11069-11078.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01277] [PMID: 27936766 ]
[5]
Lešnik, S.; Škrlj, B.; Eržen, N.; Bren, U.; Gobec, S.; Konc, J.; Janežič, D. BoBER: web interface to the base of bioisosterically exchangeable replacements. J. Cheminform., 2017, 9(1), 62.
[http://dx.doi.org/10.1186/s13321-017-0251-x] [PMID: 29234984 ]
[6]
Jukič, M.; Konc, J.; Gobec, S.; Janežič, D. Identification of conserved water sites in protein structures for drug design. J. Chem. Inf. Model., 2017, 57(12), 3094-3103.
[http://dx.doi.org/10.1021/acs.jcim.7b00443] [PMID: 29155577 ]
[7]
Bober, L.; Kawczak, P.; Bączek, T. QSAR analysis of compounds exhibiting general anesthetics’ properties. Lett. Drug Des. Discov., 2012, 9, 595-603.
[http://dx.doi.org/10.2174/157018012800673065]
[8]
Belka, M.; Konieczna, L.; Kawczak, P.; Ciesielski, T.; Slawinski, J.; Baczek, T. The chemometric evaluation of antitumor activity of novel benzensulfonamide derivatives based on their physiochemical properties. Lett. Drug Des. Discov., 2012, 3, 288-294.
[http://dx.doi.org/10.2174/157018012799129945]
[9]
Bober, L.; Kawczak, P.; Bączek, T. Pharmacological classification and activity evaluation of furan and thiophene amide derivatives applying semi-empirical ab initio molecular modeling methods. Int. J. Mol. Sci., 2012, 13(6), 6665-6678.
[http://dx.doi.org/10.3390/ijms13066665] [PMID: 22837656 ]
[10]
Stasiak, J.; Koba, M.; Bober, L.; Kawczak, P.; Baczek, T. The comparison between the calculated and hplc-predicted lipophilicity parameters for selected groups of drugs. Comb. Chem. High Throughput Screen., 2013, 16, 603-617.
[http://dx.doi.org/10.2174/1386207311316080003] [PMID: 23547602 ]
[11]
Belka, M.; Sławinski, J.; Konieczna, L.; Kawczak, P.; Ciesielski, T.; Baczek, T. Antitumor activity of novel benzensulfonamide derivatives in view of their physiochemical properties searched by principal component analysis. Med. Chem., 2013, 9(4), 517-525.
[http://dx.doi.org/10.2174/1573406411309040005] [PMID: 23140578 ]
[12]
Kawczak, P.; Bober, L.; Bączek, T. Biological activity of compounds exhibiting local anesthetics’ properties evaluated by QSAR approach. Curr. Pharm. Anal., 2014, 10, 255-262.
[http://dx.doi.org/10.2174/1573412910666140606221310]
[13]
Kawczak, P.; Bober, L.; Bączek, T. QSPR analysis of some agonists and antagonists of α-adrenergic receptors. Med. Chem. Res., 2015, 24, 372-382.
[http://dx.doi.org/10.1007/s00044-014-1130-x] [PMID: 25589825 ]
[14]
Ciura, K.; Belka, M.; Kawczak, P.; Bączek, T.; Markuszewski, M.J.; Nowakowska, J. Combined computational-experimental approach to predict blood-brain barrier (BBB) permeation based on “green” salting-out thin layer chromatography supported by simple molecular descriptors. J. Pharm. Biomed. Anal., 2017, 143, 214-221.
[http://dx.doi.org/10.1016/j.jpba.2017.05.041] [PMID: 28641198 ]
[15]
Kawczak, P.; Bober, L.; Bączek, T. Activity evaluation of some psychoactive drugs with the application of QSAR/QSPR modeling methods. Med. Chem. Res., 2018, 27(10), 2279-2286.
[http://dx.doi.org/10.1007/s00044-018-2234-5] [PMID: 30294193 ]
[16]
Kawczak, P.; Bober, L.; Bączek, T. Application of QSAR analysis and different quantum chemical calculation methods in activity evaluation of selected fluoroquinolones. Comb. Chem. High Throughput Screen., 2018, 21(7), 468-475.
[http://dx.doi.org/10.2174/1386207321666180827105856] [PMID: 30147010 ]
[17]
Kawczak, P. Bober. L.; Bączek, T. QSAR analysis of selected antimicrobial structures belonging to nitro-derivatives of heterocyclic compounds. Lett. Drug Des. Discov., 2020, 17(2), 214-224.
[http://dx.doi.org/10.2174/1570180815666181004112947]
[18]
Jensen, F. Introduction to Computational Chemistry, 3rd ed; Wiley & Sons Ltd: New York, 2017.
[19]
Lomax, C.A.; Woods, R.A. Mutant of yeast sensitive to 2,6-diaminopurine. J. Bacteriol., 1969, 100(2), 817-822.
[http://dx.doi.org/10.1128/JB.100.2.817-822.1969] [PMID: 5354948 ]
[20]
Bowen, T.L.; Whitman, W.B. Incorporation of exogenous purines and pyrimidines by Methanococcus voltae and isolation of analog-resistant mutants. Appl. Environ. Microbiol., 1987, 53(8), 1822-1826.
[http://dx.doi.org/10.1128/AEM.53.8.1822-1826.1987] [PMID: 16347408 ]
[21]
Official Gaussian Website. Available from. http://www.gaussian.com/
[22]
Caricato, M.; Scalmani, G. On the importance of the orbital relaxation in ground-state coupled cluster calculations in solution with the polarizable continuum model of solvation. J. Chem. Theory Comput., 2011, 7(12), 4012-4018.
[http://dx.doi.org/10.1021/ct2006677] [PMID: 26598347 ]
[23]
Tomasi, J.; Persico, M. Molecular interactions in solutions: an overview of methods based on continuous distributions of the solvent. Chem. Rev., 1994, 94, 2027-2094.
[http://dx.doi.org/10.1021/cr00031a013]
[24]
Tomasi, J.; Mennucci, B.; Cammi, R. Quantum mechanical continuum solvation models. Chem. Rev., 2005, 105(8), 2999-3093.
[http://dx.doi.org/10.1021/cr9904009] [PMID: 16092826 ]
[25]
Koopmans, T. Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den einzelnen Elektronen eines Atoms. Physica, 1934, 1, 104-110.
[http://dx.doi.org/10.1016/S0031-8914(34)90011-2]
[26]
Mulliken, R.S. A new electroaffinity scale, together with data on valence states and on valence ionization potentials and electron affinities. J. Chem. Phys., 1934, 2, 782-793.
[http://dx.doi.org/10.1063/1.1749394]
[27]
Mulliken, R.S. Electronic structures of molecules XI. Electroaffinity, molecular orbitals and dipole moments. J. Chem. Phys., 1935, 3, 573-785.
[http://dx.doi.org/10.1063/1.1749731]
[28]
Pearson, R.G. Absolute electronegativity and hardness correlated with molecular orbital theory. Proc. Natl. Acad. Sci. USA, 1986, 83(22), 8440-8441.
[http://dx.doi.org/10.1073/pnas.83.22.8440] [PMID: 16578791 ]
[29]
Parr, R.G.; Pearson, R.G. Absolute hardness: companion parameter to absolute electronegativity. J. Am. Chem. Soc., 1983, 105, 7512-7516.
[http://dx.doi.org/10.1021/ja00364a005]
[30]
Robles, J.; Bartolotti, L.J. Electronegativities, electron affinities, ionization potentials, and hardnesses of the elements within spin polarized density functional theory. J. Am. Chem. Soc., 1984, 106, 3723-3727.
[http://dx.doi.org/10.1021/ja00325a003]
[31]
Gross, J.H. Mass Spectrometry. A Textbook, 2. Principles of Ionization and Ion Dissociation; Springer-Verlag: Berlin, Heidelberg, 2011, pp. 21-66.
[32]
Takahata, Y.; Chong, D.P. Density-functional calculations of molecular electron affinities. J. Braz. Chem. Soc., 1999, 10, 354-358.
[http://dx.doi.org/10.1590/S0103-50531999000500003]
[33]
Dragon 7 molecular descriptors. Available from: https://chm.kode-solutions. net/products _dragon.php
[34]
Todeschini, R.; Consonni, V. Molecular Descriptors for Chemoinformatics: Volume I: Al-phabetical Listing/Volume II: Appendices, References;, Wiley-VCH Verlag GmbH & Co. KGaA:: Weinheim. 2010.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 2
Year: 2020
Page: [93 - 103]
Pages: 11
DOI: 10.2174/1573409915666190206212024
Price: $65

Article Metrics

PDF: 12
HTML: 4