Abstract
Background: The fragment-to-fragment approach for the estimation of the biological affinity of the pharmacophores with biologically active molecules has been proposed. It is the next step in the elaboration of molecular docking and using the quantum-chemical methods for the complex modeling of pharmacophores with biomolecule fragments.
Methods: The parameter φ 0 was used to estimate the contribution of π-electron interactions in biological affinity. It is directly related to the position of the frontier levels and reflects the donor-acceptor properties of the pharmacophores and stabilization energy of the [Pharm꞉BioM] complex
Results: By using quantum-chemical calculations, it was found that the stacking interaction of oxazoles with phenylalanine is 7-11 kcal/mol, while the energy of hydrogen bonding of oxazoles with the amino group of lysine is 5-9 kcal/mol. The fragment-to-fragment approach can be applied for the investigation of the dependence of biological affinity on the electronic structure of pharmacophores.c
Conclusion: The founded quantum-chemical regularities are confirmed with the structure-activity relationships of substituted oxazoles
Keywords: Biological affinity φ0, 1, 3-oxazoles, fragment-to-fragment approach, [Pharm꞉BioM] complex, π-stacking interaction, hydrogen bonds.
Graphical Abstract
[1]
Kakkar, S.; Narasimhan, B. A comprehensive review on biological activities of oxazole derivatives. BMC Chem., 2019, 13(1), 16.
[http://dx.doi.org/10.1186/s13065-019-0531-9] [PMID: 31384765]
[http://dx.doi.org/10.1186/s13065-019-0531-9] [PMID: 31384765]
[2]
Semenyuta, I.; Kovalishyn, V.; Tanchuk, V.; Pilyo, S.; Zyabrev, V.; Blagodatnyy, V.; Trokhimenko, O.; Brovarets, V.; Metelytsia, L. 1,3-Oxazole derivatives as potential anticancer agents: Computer modeling and experimental study. Comput. Biol. Chem., 2016, 65, 8-15.
[http://dx.doi.org/10.1016/j.compbiolchem.2016.09.012] [PMID: 27684433]
[http://dx.doi.org/10.1016/j.compbiolchem.2016.09.012] [PMID: 27684433]
[3]
Murphy, G.J.; Holder, J.C. PPAR-γ agonists: Therapeutic role in diabetes, inflammation and cancer. Trends Pharmacol. Sci., 2000, 21(12), 469-474.
[http://dx.doi.org/10.1016/S0165-6147(00)01559-5] [PMID: 11121836]
[http://dx.doi.org/10.1016/S0165-6147(00)01559-5] [PMID: 11121836]
[4]
Sasse, F.; Steinmetz, H.; Schupp, T.; Petersen, F.; Memmert, K.; Hofmann, H.; Heusser, C.; Brinkmann, V.; von Matt, P.; Höfle, G.; Reich-enbach, H. Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological properties. J. Antibiot. (Tokyo), 2002, 55(6), 543-551.
[http://dx.doi.org/10.7164/antibiotics.55.543] [PMID: 12195959]
[http://dx.doi.org/10.7164/antibiotics.55.543] [PMID: 12195959]
[5]
Komen, C.M.D. Ylides and imines of phosphorus A.W. Johnson John Wiley & Sons Ltd, Chichester. Recl. Trav. Chim. Pays Bas, 2010, 113(7-8), 382-587.
[http://dx.doi.org/10.1002/recl.19941130713]
[http://dx.doi.org/10.1002/recl.19941130713]
[6]
Liu, X.; Bai, L.; Pan, C.; Song, B.; Zhu, H. Novel 5-Methyl-2-[(un)substituted phenyl]-4-{4,5-dihydro- 3-[(un)substituted phenyl]-5-(1,2,3,4-tetrahydroisoquinoline-2-yl)pyrazol-1-yl}-oxazole derivatives: synthesis and anticancer activity. Chin. J. Chem., 2009, 27(10), 1957-1961.
[http://dx.doi.org/10.1002/cjoc.200990329]
[http://dx.doi.org/10.1002/cjoc.200990329]
[7]
Chen, J.; Li, C-M.; Wang, J.; Ahn, S.; Wang, Z.; Lu, Y.; Dalton, J.T.; Miller, D.D.; Li, W. Synthesis and antiproliferative activity of novel 2-aryl-4-benzoyl-imidazole derivatives targeting tubulin polymerization. Bioorg. Med. Chem., 2011, 19(16), 4782-4795.
[http://dx.doi.org/10.1016/j.bmc.2011.06.084] [PMID: 21775150]
[http://dx.doi.org/10.1016/j.bmc.2011.06.084] [PMID: 21775150]
[8]
Kachaeva, M.V.; Hodyna, D.M.; Semenyuta, I.V.; Pilyo, S.G.; Prokopenko, V.M.; Kovalishyn, V.V.; Metelytsia, L.O.; Brovarets, V.S. Design, synthesis and evaluation of novel sulfonamides as potential anticancer agents. Comput. Biol. Chem., 2018, 74, 294-303.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.04.006] [PMID: 29698921]
[http://dx.doi.org/10.1016/j.compbiolchem.2018.04.006] [PMID: 29698921]
[9]
Cameron, D.M.; Thompson, J.; March, P.E.; Dahlberg, A.E. Initiation factor IF2, thiostrepton and micrococcin prevent the binding of elongation factor G to the Escherichia coli ribosome. J. Mol. Biol., 2002, 319(1), 27-35.
[http://dx.doi.org/10.1016/S0022-2836(02)00235-8] [PMID: 12051934]
[http://dx.doi.org/10.1016/S0022-2836(02)00235-8] [PMID: 12051934]
[10]
Rodnina, M.V.; Savelsbergh, A.; Matassova, N.B.; Katunin, V.I.; Semenkov, Y.P.; Wintermeyer, W. Thiostrepton inhibits the turnover but not the GTPase of elongation factor G on the ribosome. Proc. Natl. Acad. Sci. USA, 1999, 96(17), 9586-9590.
[http://dx.doi.org/10.1073/pnas.96.17.9586] [PMID: 10449736]
[http://dx.doi.org/10.1073/pnas.96.17.9586] [PMID: 10449736]
[11]
Lawrence, D.S.; Copper, J.E.; Smith, C.D. Structure-activity studies of substituted quinoxalinones as multiple-drug-resistance antagonists. J. Med. Chem., 2001, 44(4), 594-601.
[http://dx.doi.org/10.1021/jm000282d] [PMID: 11170649]
[http://dx.doi.org/10.1021/jm000282d] [PMID: 11170649]
[12]
Borst, P. Multidrug resistance: A solvable problem? Ann. Oncol., 1999, 10(4)(Suppl. 4), 162-164.
[http://dx.doi.org/10.1093/annonc/10.suppl_4.S162] [PMID: 10436813]
[http://dx.doi.org/10.1093/annonc/10.suppl_4.S162] [PMID: 10436813]
[13]
Tomi, I.H.R.; Al-Qaisi, A.H.J.; Al-Qaisi, Z.H.J. Synthesis, characterization and effect of bis-1,3,4-oxadiazole rings containing glycine moi-ety on the activity of some transferase enzymes. J. King Saud Univ. Sci., 2011, 23(1), 23-33.
[http://dx.doi.org/10.1016/j.jksus.2010.06.002]
[http://dx.doi.org/10.1016/j.jksus.2010.06.002]
[14]
Kumar, A.; Ahmad, P.; Maurya, R.A.; Singh, A.B.; Srivastava, A.K. Novel 2-aryl-naphtho[1,2-d]oxazole derivatives as potential PTP-1B inhibitors showing antihyperglycemic activities. Eur. J. Med. Chem., 2009, 44(1), 109-116.
[http://dx.doi.org/10.1016/j.ejmech.2008.03.009] [PMID: 18436346]
[http://dx.doi.org/10.1016/j.ejmech.2008.03.009] [PMID: 18436346]
[15]
Malamas, M.S.; Sredy, J.; Moxham, C.; Katz, A.; Xu, W.; McDevitt, R.; Adebayo, F.O.; Sawicki, D.R.; Seestaller, L.; Sullivan, D.; Taylor, J.R. Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties. J. Med. Chem., 2000, 43(7), 1293-1310.
[http://dx.doi.org/10.1021/jm990560c] [PMID: 10753467]
[http://dx.doi.org/10.1021/jm990560c] [PMID: 10753467]
[16]
Malamas, M.S.; Sredy, J.; Gunawan, I.; Mihan, B.; Sawicki, D.R.; Seestaller, L.; Sullivan, D.; Flam, B.R. New azolidinediones as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties. J. Med. Chem., 2000, 43(5), 995-1010.
[http://dx.doi.org/10.1021/jm990476x] [PMID: 10715163]
[http://dx.doi.org/10.1021/jm990476x] [PMID: 10715163]
[17]
Kachaeva, M.V.; Hodyna, D.M.; Obernikhina, N.V.; Pilyo, S.G.; Kovalenko, Y.S.; Prokopenko, V.M.; Kachkovsky, O.D.; Brovarets, V.S. Dependence of the anticancer activity of 1,3-oxazole derivatives on the donor/acceptor nature of his substitues. J. Heterocycl. Chem., 2019, 56, 3122-3134.
[http://dx.doi.org/10.1002/jhet.3711]
[http://dx.doi.org/10.1002/jhet.3711]
[18]
Kachaeva, M.; Kachaeva, M.V.; Obernikhina, N.V.; Veligina, E.S.; Zhuravlova, M.Yu.; Prostota, Ya.O.; Kachkovsky, O.D.; Brovarets, V.S. Estimation of biological affinity of nitrogen-containing conjugated heterocyclic pharmacophores. Chem. Heterocycl. Compd., 2019, 55(4/5), 448-454.
[http://dx.doi.org/10.1007/s10593-019-02478-6]
[http://dx.doi.org/10.1007/s10593-019-02478-6]
[19]
Kachaeva, M.V.; Pilyo, S.G.; Zhirnov, V.V.; Brovarets, V.S. Synthesis, characterization, and in vitro anticancer evaluation of 2-substituted 5-arylsulfonyl-1,3-oxazole-4-carbonitriles. Med. Chem. Res., 2018, 28, 71-80.
[http://dx.doi.org/10.1007/s00044-018-2265-y]
[http://dx.doi.org/10.1007/s00044-018-2265-y]
[20]
Murugavel, S.; Ravikumar, C.; Jaabil, G.; Alagusundaram, P. 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., 2019, 1176, 729-742.
[http://dx.doi.org/10.1016/j.molstruc.2018.09.010]
[http://dx.doi.org/10.1016/j.molstruc.2018.09.010]
[21]
Christensen, C.; Bruun Schiødt, C.; Tækker Foged, N.; Meldal, M. Solid phase combinatorial library of 1,3-azole containing peptides for the discovery of matrix metallo proteinase inhibitors. Mol. Inform., 2003, 22(7), 754-766.
[http://dx.doi.org/10.1002/qsar.200320006]
[http://dx.doi.org/10.1002/qsar.200320006]
[22]
Mortenson, P.N.; Erlanson, D.A.; de Esch, I.J.P.; Jahnke, W.; Johnson, C.N. Fragment-to-lead medicinal chemistry publications in 2017. J. Med. Chem., 2019, 62(8), 3857-3872.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01472] [PMID: 30462504]
[http://dx.doi.org/10.1021/acs.jmedchem.8b01472] [PMID: 30462504]
[23]
de Souza Neto, L.R.; Moreira-Filho, J.T.; Neves, B.J.; Maidana, R.L.B.R.; Guimarães, A.C.R.; Furnham, N.; Andrade, C.H.; Silva, F.P., Jr In silico strategies to support fragment-to-lead optimization in drug discovery. Front Chem., 2020, 8, 93.
[http://dx.doi.org/10.3389/fchem.2020.00093] [PMID: 32133344]
[http://dx.doi.org/10.3389/fchem.2020.00093] [PMID: 32133344]
[24]
Burley, S.K.; Petsko, G.A. Aromatic-aromatic interaction: A mechanism of protein structure stabilization. Science, 1985, 229(4708), 23-28.
[http://dx.doi.org/10.1126/science.3892686] [PMID: 3892686]
[http://dx.doi.org/10.1126/science.3892686] [PMID: 3892686]
[25]
Hunter, C.A. Meldola Lecture. The role of aromatic interactions in molecular recognition. Chem. Soc. Rev., 1994, 23(2), 101-109.
[http://dx.doi.org/10.1039/cs9942300101]
[http://dx.doi.org/10.1039/cs9942300101]
[26]
Kim, K.S.; Tarakeshwar, P.; Lee, J.Y. Molecular clusters of π-systems: Theoretical studies of structures, spectra, and origin of interaction energies. Chem. Rev., 2000, 100(11), 4145-4186.
[http://dx.doi.org/10.1021/cr990051i] [PMID: 11749343]
[http://dx.doi.org/10.1021/cr990051i] [PMID: 11749343]
[27]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E. All, GAUSSIAN 09; revision A.02; Gaussian, Inc.: Wallingford, CT, 2016.
[28]
Zunszain, P.A.; Ghuman, J.; McDonagh, A.F.; Curry, S. Crystallographic analysis of human serum albumin complexed with 4Z,15E-bilirubin-IXalpha. J. Mol. Biol., 2008, 381(2), 394-406.
[http://dx.doi.org/10.1016/j.jmb.2008.06.016] [PMID: 18602119]
[http://dx.doi.org/10.1016/j.jmb.2008.06.016] [PMID: 18602119]
[29]
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]
[http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]
[30]
Accelrys Software Inc. Discovery Studio Modeling Environment, Release 3.5; Accelrys Software Inc.: San Diego, 2002.
[31]
Velihina, E.S.; Obernikhina, N.V.; Pilyo, S.G.; Kachkovsky, O.D.; Brovarets, V.S. Synthesis, electronic structure and anti-cancer activity of the phenyl substituted pyrazolo[1,5-a][1,3,5]triazines. Curr. Org. Chem., 2021, 25(12), 1441-1454.
[http://dx.doi.org/10.2174/1385272825666210607004536]
[http://dx.doi.org/10.2174/1385272825666210607004536]
[32]
Obernikhina, N.; Kachaeva, M.; Shchodryi, V.; Prostota, Y.; Kachkovsky, O.; Brovarets, V.; Tkachuk, Z. Topological index of conjugated heterocyclic compounds as their donor/acceptor parameter. Polycycl. Aromat. Compd., 2020, 40(4), 1196-1209.
[http://dx.doi.org/10.1080/10406638.2018.1538056]
[http://dx.doi.org/10.1080/10406638.2018.1538056]
[33]
Obernikhina, N.; Pavlenko, O.; Kachkovsky, A.; Brovarets, V. Quantum-chemical and experimental estimation of non-bonding level (fer-mi level) and π-electron afinity of conjugated systems. Polycycl. Aromat. Compd., 2021, 41(10), 2110-2119.
[http://dx.doi.org/10.1080/10406638.2019.1710855]
[http://dx.doi.org/10.1080/10406638.2019.1710855]
[34]
Obernikhina, N.; Obernikhina, N.; Zhuravlova, M.; Kachkovsky, O.; Kobzar, O.; Brovarets, V.; Pavlenko, O.; Kulish, M.; Dmytrenko, O. Stability of fullerene complexes with oxazoles as biologically active compounds. Appl. Nanosci., 2020, 10, 1345-1353.
[http://dx.doi.org/10.1007/s13204-019-01225-9]
[http://dx.doi.org/10.1007/s13204-019-01225-9]
[36]
Boyd, M.R.; Paull, K.D. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res., 1995, 34, 91-109.
[http://dx.doi.org/10.1002/ddr.430340203]
[http://dx.doi.org/10.1002/ddr.430340203]
[37]
Pardini, B.; Kumar, R.; Naccarati, A.; Novotny, J.; Prasad, R.B.; Forsti, A.; Hemminki, K.; Vodicka, P.; Lorenzo Bermejo, J. 5-Fluorouracil-based chemotherapy for colorectal cancer and MTHFR/MTRR genotypes. Br. J. Clin. Pharmacol., 2011, 72(1), 162-163.
[http://dx.doi.org/10.1111/j.1365-2125.2010.03892.x] [PMID: 21204909]
[http://dx.doi.org/10.1111/j.1365-2125.2010.03892.x] [PMID: 21204909]
[38]
Velihina, Ye.; Scattolin, T.; Bondar, D.; Pil’o, S.; Obernikhina, N.; Kachkovskyi, D.; Semenyuta, I.; Caligiuri, I.; Rizzolio, F.; Brovarets, S.; Karpichev, Ye.; Nolan, St.P. Synthesis, in silico and in vitro evaluation of novel oxazolopyrimidines as promising anticancer agents. Helv. Chim. Acta, 2020, 103(12)e2000169
[http://dx.doi.org/10.1002/hlca.202000169]
[http://dx.doi.org/10.1002/hlca.202000169]
[39]
Almutairi, M.S.; Hegazy, G.H.; Haiba, M.E.; Ali, H.I.; Khalifa, N.M. Soliman, Ael-M. Synthesis, docking and biological activities of novel hybrids celecoxib and anthraquinone analogs as potent cytotoxic agents. Int. J. Mol. Sci., 2014, 15(12), 22580-22603.
[http://dx.doi.org/10.3390/ijms151222580] [PMID: 25490139]
[http://dx.doi.org/10.3390/ijms151222580] [PMID: 25490139]
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