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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Synthesis, Molecular Modelling and Biological Studies of 3-hydroxypyrane- 4-one and 3-hydroxy-pyridine-4-one Derivatives as HIV-1 Integrase Inhibitors

Author(s): Hajar Sirous, Afshin Fassihi*, Simone Brogi*, Giuseppe Campiani, Frauke Christ, Zeger Debyser, Sandra Gemma, Stefania Butini, Giulia Chemi, Alessandro Grillo, Rezvan Zabihollahi, Mohammad R. Aghasadeghi, Lotfollah Saghaie and Hamid R. Memarian

Volume 15, Issue 7, 2019

Page: [755 - 770] Pages: 16

DOI: 10.2174/1573406415666181219113225

Price: $65

Abstract

Background: Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against HIV, for avoiding the drug resistance issue.

Objective: To develop novel HIV-1 IN inhibitors, a series of 3-hydroxy-pyrane-4-one (HP) and 3- hydroxy-pyridine-4-one (HPO) derivatives have been rationally designed and synthesized.

Methods: To provide a significant characterization of the novel compounds, in-depth computational analysis was performed using a novel HIV-1 IN/DNA binary 3D-model for investigating the binding mode of the newly conceived molecules in complex with IN. The 3D-model was generated using the proto-type foamy virus (PFV) DNA as a structural template, positioning the viral polydesoxyribonucleic chain into the HIV-1 IN homology model. Moreover, a series of in vitro tests were performed including HIV-1 activity inhibition, HIV-1 IN activity inhibition, HIV-1 IN strand transfer activity inhibition and cellular toxicity.

Results: Bioassay results indicated that most of HP analogues including HPa, HPb, HPc, HPd, HPe and HPg, showed favorable inhibitory activities against HIV-1-IN in the low micromolar range. Particularly halogenated derivatives (HPb and HPd) offered the best biological activities in terms of reduced toxicity and optimum inhibitory activities against HIV-1 IN and HIV-1 in cell culture.

Conclusion: Halogenated derivatives, HPb and HPd, displayed the most promising anti-HIV profile, paving the way to the optimization of the presented scaffolds for developing new effective antiviral agents.

Keywords: 3-hydroxy-pyrane-4-one, 3-hydroxy-pyridine-4-one, halogenated derivatives, HIV-1 IN inhibitors (HIV-1 INIs), molecular modelling, anti-HIV agents.

Graphical Abstract
[1]
WHO Fact Sheet No 360 Updated November 2016. Available at: http://www.who.int/mediacentre/factsheets/fs360/en/ Accessed 8 January 2018.
[2]
FDA (2017) Antiretroviral drugs used in the treatment of HIV infection. Available at: https://www.fda.gov/ForPatients/Illness/HIVAIDS/Treatment/ucm118915.htm Accessed 8 January 2018.
[3]
Dayam, R.; Al-Mawsawi, L.Q.; Neamati, N. HIV-1 integrase inhibitors: An emerging clinical reality. Drugs R D., 2007, 8, 155-168.
[4]
Dubey, S.; Satyanarayana, Y.D.; Lavania, H. Development of integrase inhibitors for treatment of AIDS: An overview. Eur. J. Med. Chem., 2007, 42, 1159-1168.
[5]
Debyser, Z.; Cherepanov, P.; Van Maele, B.; De Clercq, E.; Witvrouw, M. In search of authentic inhibitors of HIV-1 integration. Antivir. Chem. Chemother., 2002, 13, 1-15.
[6]
Chiu, T.K.; Davies, D.R. Structure and function of HIV-1 integrase. Curr. Top. Med. Chem., 2004, 4, 965-977.
[7]
Pommier, Y.; Johnson, A.A.; Marchand, C. Integrase inhibitors to treat HIV/AIDS. Nat. Rev. Drug Discov., 2005, 4, 236-248.
[8]
Neamati, N.; Lin, Z.; Karki, R.G.; Orr, A.; Cowansage, K.; Strumberg, D.; Pais, G.C.; Voigt, J.H.; Nicklaus, M.C.; Winslow, H.E.; Zhao, H.; Turpin, J.A.; Yi, J.; Skalka, A.M.; Burke, T.R. Jr.; Pommier, Y. Metal-dependent inhibition of HIV-1 integrase. J. Med. Chem., 2002, 45, 5661-5670.
[9]
Dyda, F.; Hickman, A.B.; Jenkins, T.M.; Engelman, A.; Craigie, R.; Davies, D.R. Crystal structure of the catalytic domain of HIV-1 integrase: Similarity to other polynucleotidyl transferases. Science, 1994, 266, 1981-1986.
[10]
McColl, D.J.; Chen, X. Strand transfer inhibitors of HIV-1 integrase: Bringing in a new era of antiretroviral therapy. Antiviral Res., 2010, 85, 101-118.
[11]
Grobler, J.A.; Stillmock, K.; Hu, B.; Witmer, M.; Felock, P.; Espeseth, A.S.; Wolfe, A.; Egbertson, M.; Bourgeois, M.; Melamed, J.; Wai, J.S.; Young, S.; Vacca, J.; Hazuda, D.J. Diketo acid inhibitor mechanism and HIV-1 integrase: Implications for metal binding in the active site of phosphotransferase enzymes. Proc. Natl. Acad. Sci. USA, 2002, 99, 6661-6666.
[12]
Espeseth, A.S.; Felock, P.; Wolfe, A.; Witmer, M.; Grobler, J.; Anthony, N.; Egbertson, M.; Melamed, J.Y.; Young, S.; Hamill, T.; Cole, J.L.; Hazuda, D.J. HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proc. Natl. Acad. Sci. USA, 2000, 97, 11244-11249.
[13]
Kawasuji, T.; Fuji, M.; Yoshinaga, T.; Sato, A.; Fujiwara, T.; Kiyama, R. A platform for designing HIV integrase inhibitors. Part 2: A two-metal binding model as a potential mechanism of HIV integrase inhibitors. Bioorg. Med. Chem., 2006, 14, 8420-8429.
[14]
Johns, B.A.; Svolto, A.C. Advances in two-metal chelation inhibitors of HIV integrase. Expert Opin. Ther. Pat., 2008, 18, 1225-1237.
[15]
Kawasuji, T.; Yoshinaga, T.; Sato, A.; Yodo, M.; Fujiwara, T.; Kiyama, R. A platform for designing HIV integrase inhibitors. Part 1: 2-hydroxy-3-heteroaryl acrylic acid derivatives as novel HIV integrase inhibitor and modeling of hydrophilic and hydrophobic pharmacophores. Bioorg. Med. Chem., 2006, 14, 8430-8445.
[16]
Rowley, M. The discovery of raltegravir, an integrase inhibitor for the treatment of HIV infection. Prog. Med. Chem., 2008, 46, 1-28.
[17]
Summa, V.; Petrocchi, A.; Bonelli, F.; Crescenzi, B.; Donghi, M.; Ferrara, M.; Fiore, F.; Gardelli, C.; Gonzalez Paz, O.; Hazuda, D.J.; Jones, P.; Kinzel, O.; Laufer, R.; Monteagudo, E.; Muraglia, E.; Nizi, E.; Orvieto, F.; Pace, P.; Pescatore, G.; Scarpelli, R.; Stillmock, K.; Witmer, M.V.; Rowley, M. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem., 2008, 51, 5843-5855.
[18]
Sato, M.; Kawakami, H.; Motomura, T.; Aramaki, H.; Matsuda, T.; Yamashita, M.; Ito, Y.; Matsuzaki, Y.; Yamataka, K.; Ikeda, S.; Shinkai, H. Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors. J. Med. Chem., 2009, 52, 4869-4882.
[19]
Shimura, K.; Kodama, E.; Sakagami, Y.; Matsuzaki, Y.; Watanabe, W.; Yamataka, K.; Watanabe, Y.; Ohata, Y.; Doi, S.; Sato, M.; Kano, M.; Ikeda, S.; Matsuoka, M. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J. Virol., 2008, 82, 764-774.
[20]
Katlama, C.; Murphy, R. Dolutegravir for the treatment of HIV. Expert Opin. Investig. Drugs, 2012, 21, 523-530.
[21]
Santos, M.A.; Marques, S.M.; Chaves, S. Hydroxypyridinones as “privileged” chelating structures for the design of medicinal drugs. Coord. Chem. Rev., 2012, 256, 240-259.
[22]
Sirous, H.; Zabihollahi, R.; Aghasadeghi, M.R.; Sadat, S.M.; Saghaie, L.; Fassihi, A. Docking studies of some 5-hydroxypyridine-4-one derivatives: Evaluation of integrase and ribonuclease H domain of reverse transcriptase as possible targets for anti-HIV-1 activity. Med. Chem. Res., 2015, 24, 2195-2212.
[23]
Rostami, M.; Sirous, H.; Zabihollahi, R.; Aghasadeghi, M.R.; Sadat, S.M.; Namazi, R.; Saghaie, L.; Memarian, H.R.; Fassihi, A. Design, synthesis and anti-HIV-1 evaluation of a series of 5-hydroxypyridine-4-one derivatives as possible integrase inhibitors. Med. Chem. Res., 2015, 24, 4113-4127.
[24]
Kawasuji, T.; Johns, B.A.; Yoshida, H.; Taishi, T.; Taoda, Y.; Murai, H.; Kiyama, R.; Fuji, M.; Yoshinaga, T.; Seki, T.; Kobayashi, M.; Sato, A.; Fujiwara, T. Carbamoyl pyridone HIV-1 integrase inhibitors. 1. Molecular design and establishment of an advanced two-metal binding pharmacophore. J. Med. Chem., 2012, 55, 8735-8744.
[25]
Marchand, C.; Zhang, X.; Pais, G.C.; Cowansage, K.; Neamati, N.; Burke, T.R. Jr.; Pommier, Y. Structural determinants for HIV-1 integrase inhibition by beta-diketo acids. J. Biol. Chem., 2002, 277, 12596-12603.
[26]
DeAnda, F.; Hightower, K.E.; Nolte, R.T.; Hattori, K.; Yoshinaga, T.; Kawasuji, T.; Underwood, M.R. Dolutegravir interactions with HIV-1 integrase-DNA: Structural rationale for drug resistance and dissociation kinetics. PLoS One, 2013, 8e77448
[27]
Cappelli, A.; Manini, M.; Valenti, S.; Castriconi, F.; Giuliani, G.; Anzini, M.; Brogi, S.; Butini, S.; Gemma, S.; Campiani, G.; Giorgi, G.; Mennuni, L.; Lanza, M.; Giordani, A.; Caselli, G.; Letari, O.; Makovec, F. Synthesis and structure-activity relationship studies in serotonin 5-HT(1A) receptor agonists based on fused pyrrolidone scaffolds. Eur. J. Med. Chem., 2013, 63, 85-94.
[28]
Giovani, S.; Penzo, M.; Brogi, S.; Brindisi, M.; Gemma, S.; Novellino, E.; Savini, L.; Blackman, M.J.; Campiani, G.; Butini, S. Rational design of the first difluorostatone-based PfSUB1 inhibitors. Bioorg. Med. Chem. Lett., 2014, 24, 3582-35866.
[29]
Gemma, S.; Brogi, S.; Patil, P.R.; Giovani, S.; Lamponi, S.; Cappelli, A.; Novellino, E.; Brown, A.; Higgins, M.K.; Mustafa, K.; Szestak, T.; Craig, A.G.; Campiani, G.; Butini, S.; Brindisi, M. From (+)-epigallocatechin gallate to a simplified synthetic analogue as a cytoadherence inhibitor for P. falciparum. Rsc Adv., 2014, 4, 4769-4781.
[30]
Brogi, S.; Giovani, S.; Brindisi, M.; Gemma, S.; Novellino, E.; Campiani, G.; Blackman, M.J.; Butini, S. In silico study of subtilisin-like protease 1 (SUB1) from different Plasmodium species in complex with peptidyl-difluorostatones and characterization of potent pan-SUB1 inhibitors. J. Mol. Graph. Model., 2016, 64, 121-130.
[31]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47, 1739-1749.
[32]
Glide. Version 5.7; Schrödinger, LLC: New York, NY, 2011.
[33]
Schrödinger, Suite. 2011 QM-Polarized Ligand Docking protocol: Glide. Version 5.7. Schrödinger, LLC, New York, NY,2011; Jaguar. Version 7.8. Schrödinger, LLC, New York, NY,2011; QSite. Version 5.7; Schrödinger, LLC: New York, NY, 2011.
[34]
Paolino, M.; Brindisi, M.; Vallone, A.; Butini, S.; Campiani, G.; Nannicini, C.; Giuliani, G.; Anzini, M.; Lamponi, S.; Giorgi, G.; Sbardella, D.; Ferraris, D.M.; Marini, S.; Coletta, M.; Palucci, I.; Minerva, M.; Delogu, G.; Pepponi, I.; Goletti, D.; Cappelli, A.; Gemma, S.; Brogi, S. Development of potent inhibitors of the mycobacterium tuberculosis virulence factor ZMP1 and evaluation of their effect on mycobacterial survival inside macrophages. ChemMedChem, 2018, 13, 422-430.
[35]
Brindisi, M.; Gemma, S.; Kunjir, S.; Di Cerbo, L.; Brogi, S.; Parapini, S.; D’Alessandro, S.; Taramelli, D.; Habluetzel, A.; Tapanelli, S.; Lamponi, S.; Novellino, E.; Campiani, G.; Butini, S. Synthetic spirocyclic endoperoxides: New antimalarial scaffolds. MedChemComm, 2015, 6, 357-362.
[36]
Brindisi, M.; Brogi, S.; Relitti, N.; Vallone, A.; Butini, S.; Gemma, S.; Novellino, E.; Colotti, G.; Angiulli, G.; Di Chiaro, F.; Fiorillo, A.; Ilari, A.; Campiani, G. Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking. Sci. Rep., 2015, 5, 9705.
[37]
Gasser, A.; Brogi, S.; Urayama, K.; Nishi, T.; Kurose, H.; Tafi, A.; Ribeiro, N.; Desaubry, L.; Nebigil, C.G. Discovery and cardioprotective effects of the first non-Peptide agonists of the G protein-coupled prokineticin receptor-1. PLoS One, 2015, 10e0121027
[38]
Brogi, S.; Butini, S.; Maramai, S.; Colombo, R.; Verga, L.; Lanni, C.; De Lorenzi, E.; Lamponi, S.; Andreassi, M.; Bartolini, M.; Andrisano, V.; Novellino, E.; Campiani, G.; Brindisi, M.; Gemma, S. Disease-modifying Anti-Alzheimer’s drugs: Inhibitors of human cholinesterases interfering with beta-amyloid aggregation. CNS Neurosci. Ther., 2014, 20, 624-632.
[39]
Brogi, S.; Fiorillo, A.; Chemi, G.; Butini, S.; Lalle, M.; Ilari, A.; Gemma, S.; Campiani, G. Structural characterization of Giardia duodenalis thioredoxin reductase (gTrxR) and computational analysis of its interaction with NBDHEX. Eur. J. Med. Chem., 2017, 135, 479-490.
[40]
QikProp. Version 3.4; Schrödinger, LLC: New York, NY, 2011.
[41]
P450. Site of Metabolism Prediction. Version 1.1; Schrödinger, LLC: New York, NY, 2011.
[42]
Gemma, S.; Camodeca, C.; Sanna, C.S.; Joshi, B.P.; Bernetti, M.; Moretti, V.; Brogi, S.; Bonache de Marcos, M.C.; Savini, L.; Taramelli, D.; Basilico, N.; Parapini, S.; Rottmann, M.; Brun, R.; Lamponi, S.; Caccia, S.; Guiso, G.; Summers, R.L.; Martin, R.E.; Saponara, S.; Gorelli, B.; Novellino, E.; Campiani, G.; Butini, S. Optimization of 4-aminoquinoline/clotrimazole-based hybrid antimalarials: Further structure-activity relationships, in vivo studies, and preliminary toxicity profiling. J. Med. Chem., 2012, 55, 6948-6967.
[43]
Debyser, Z.; Cherepanov, P.; Pluymers, W.; De Clercq, E. Assays for the evaluation of HIV-1 integrase inhibitors. Methods Mol. Biol., 2001, 160, 139-155.
[44]
Christ, F.; Busschots, K.; Hendrix, J.; McNeely, M.; Engelborghs, Y.; Debyser, Z. Assays for Evaluation of HIV-1 Integrase Enzymatic Activity; DNA Binding, and Cofactor Interaction, 2011.
[45]
Hwang, Y.; Rhodes, D.; Bushman, F. Rapid microtiter assays for poxvirus topoisomerase, mammalian type IB topoisomerase and HIV-1 integrase: Application to inhibitor isolation. Nucleic Acids Res., 2000, 28, 4884-4892.
[46]
Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; Declercq, E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J. Virol. Methods, 1988, 20, 309-321.
[47]
Ellis, B.L.; Duhme, A.K.; Hider, R.C.; Hossain, M.B.; Rizvi, S.; van der Helm, D. Synthesis, physicochemical properties, and biological evaluation of hydroxypyranones and hydroxypyridinones: Novel bidentate ligands for cell-labeling. J. Med. Chem., 1996, 39, 3659-3670.
[48]
Ma, Y.; Luo, W.; Quinn, P.J.; Liu, Z.; Hider, R.C. Design, synthesis, physicochemical properties, and evaluation of novel iron chelators with fluorescent sensors. J. Med. Chem., 2004, 47, 6349-6362.
[49]
Becker, H.D. The conversion of kojic acid into comenaldehyde and comenic acid. Acta Chem. Scand., 1962, 16, 78-82.
[50]
Lindgren, B.O.; Nilsson, T. preparation of carboxylic acids from aldehydes (including hydroxylated benzaldehydes) by oxidation with chlorite. Acta Chem. Scand., 1973, 27, 888-890.
[51]
Sheehan, J.C.; Preston, J.; Cruickshank, P.A. A rapid synthesis of oligopeptide derivatives without isolation of intermediates. J. Am. Chem. Soc., 1965, 87, 2492-2493.
[52]
Puerta, D.T.; Mongan, J.; Tran, B.L.; McCammon, J.A.; Cohen, S.M. Potent, selective pyrone-based inhibitors of stromelysin-1. J. Am. Chem. Soc., 2005, 127, 14148-14149.
[53]
Harris, R.L.N. Potential wool growth inhibitors. Improved syntheses of mimosine and related 4(1H)-pyridones. Aust. J. Chem., 1976, 29, 1329-1334.
[54]
Kosak, T.M.; Conrad, H.A.; Korich, A.L.; Lord, R.L. Ether cleavage re-investigated: Elucidating the mechanism of BBr3-facilitated demethylation of aryl methyl ethers. Eur. J. Org. Chem., 2015, 2015, 7460-7467.
[55]
Engelman, A.; Craigie, R. Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J. Virol., 1992, 66, 6361-6369.
[56]
Kulkosky, J.; Jones, K.S.; Katz, R.A.; Mack, J.P.; Skalka, A.M. Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Mol. Cell. Biol., 1992, 12, 2331-2338.
[57]
Valkov, E.; Gupta, S.S.; Hare, S.; Helander, A.; Roversi, P.; McClure, M.; Cherepanov, P. Functional and structural characterization of the integrase from the prototype foamy virus. Nucleic Acids Res., 2009, 37, 243-255.
[58]
Krishnan, L.; Li, X.; Naraharisetty, H.L.; Hare, S.; Cherepanov, P.; Engelman, A. Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc. Natl. Acad. Sci. USA, 2010, 107, 15910-15915.
[59]
Tang, J.; Maddali, K.; Pommier, Y.; Sham, Y.Y.; Wang, Z. Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited. Bioorg. Med. Chem. Lett., 2010, 20, 3275-3279.
[60]
Dolan, J.; Chen, A.; Weber, I.T.; Harrison, R.W.; Leis, J. Defining the DNA substrate binding sites on HIV-1 integrase. J. Mol. Biol., 2009, 385, 568-579.
[61]
Johnson, A.A.; Marchand, C.; Patil, S.S.; Costi, R.; Di Santo, R.; Burke, T.R. Jr.; Pommier, Y. Probing HIV-1 integrase inhibitor binding sites with position-specific integrase-DNA cross-linking assays. Mol. Pharmacol., 2007, 71, 893-901.
[62]
Agapkina, J.; Smolov, M.; Barbe, S.; Zubin, E.; Zatsepin, T.; Deprez, E.; Le Bret, M.; Mouscadet, J.F.; Gottikh, M. Probing of HIV-1 integrase/DNA interactions using novel analogs of viral DNA. J. Biol. Chem., 2006, 281, 11530-11540.
[63]
Adesokan, A.A.; Roberts, V.A.; Lee, K.W.; Lins, R.D.; Briggs, J.M. Prediction of HIV-1 integrase/viral DNA interactions in the catalytic domain by fast molecular docking. J. Med. Chem., 2004, 47, 821-828.
[64]
Dirac, A.M.; Kjems, J. Mapping DNA-binding sites of HIV-1 integrase by protein footprinting. Eur. J. Biochem., 2001, 268, 743-751.
[65]
Hare, S.; Vos, A.M.; Clayton, R.F.; Thuring, J.W.; Cummings, M.D.; Cherepanov, P. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc. Natl. Acad. Sci. USA, 2010, 107, 20057-20062.
[66]
Hare, S.; Gupta, S.S.; Valkov, E.; Engelman, A.; Cherepanov, P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature, 2010, 464, 232-236.
[67]
Hare, S.; Smith, S.J.; Metifiot, M.; Jaxa-Chamiec, A.; Pommier, Y.; Hughes, S.H.; Cherepanov, P. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol. Pharmacol., 2011, 80, 565-572.
[68]
Available at: http://mordred.bioc.cam.ac.uk/~rapper/rampage.php Accessed June 2017.
[69]
Lovell, S.C.; Davis, I.W.; Arendall, W.B., III; de Bakker, P.I.; Word, J.M.; Prisant, M.G.; Richardson, J.S.; Richardson, D.C. Structure validation by Calpha geometry: Phi, psi and Cbeta deviation. Proteins, 2003, 50, 437-450.
[70]
Luthy, R.; Bowie, J.U.; Eisenberg, D. Assessment of protein models with three-dimensional profiles. Nature, 1992, 356, 83-85.
[71]
Lins, R.D.; Adesokan, A.; Soares, T.A.; Briggs, J.M. Investigations on human immunodeficiency virus type 1 integrase/DNA binding interactions via molecular dynamics and electrostatics calculations. Pharmacol. Ther., 2000, 85, 123-131.
[72]
Illingworth, C.J.R.; Morris, G.M.; Parkes, K.E.B.; Snell, C.R.; Reynolds, C.A. Assessing the role of polarization in docking. J. Phys. Chem. A, 2008, 112, 12157-12163.
[73]
Cho, A.E.; Guallar, V.; Berne, B.J.; Friesner, R. Importance of accurate charges in molecular docking: Quantum mechanical/molecular mechanical (QM/MM) approach. J. Comput. Chem., 2005, 26, 915-931.
[74]
Agrawal, A.; DeSoto, J.; Fullagar, J.L.; Maddali, K.; Rostami, S.; Richman, D.D.; Pommier, Y.; Cohen, S.M. Probing chelation motifs in HIV integrase inhibitors. Proc. Natl. Acad. Sci. USA, 2012, 109, 2251-2256.
[75]
Metifiot, M.; Marchand, C.; Maddali, K.; Pommier, Y. Resistance to integrase inhibitors. Viruses, 2010, 2, 1347-1366.
[76]
Pearlman, D.A.; Charifson, P.S. Are free energy calculations useful in practice? A comparison with rapid scoring functions for the p38 MAP kinase protein system. J. Med. Chem., 2001, 44, 3417-3423.
[77]
Taylor, R.D.; Jewsbury, P.J.; Essex, J.W. A review of protein-small molecule docking methods. J. Comput. Aided Mol. Des., 2002, 16, 151-166.
[78]
Kuhn, B.; Kollman, P.A. Binding of a diverse set of ligands to avidin and streptavidin: An accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models. J. Med. Chem., 2000, 43, 3786-3791.
[79]
Huang, N.; Kalyanaraman, C.; Irwin, J.J.; Jacobson, M.P. Physics-based scoring of protein-ligand complexes: Enrichment of known inhibitors in large-scale virtual screening. J. Chem. Inf. Model., 2006, 46, 243-253.
[80]
Liu, Z.D.; Piyamongkol, S.; Liu, D.Y.; Khodr, H.H.; Lu, S.L.; Hider, R.C. Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: Novel iron chelators with enhanced pFe3+ values. Bioorg. Med. Chem., 2001, 9, 563-573.
[81]
Billamboz, M.; Suchaud, V.; Bailly, F.; Lion, C.; Demeulemeester, J.; Calmels, C.; Andreola, M.L.; Christ, F.; Debyser, Z.; Cotelle, P. 4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel class of HIV-1 integrase inhibitors. ACS Med. Chem. Lett., 2013, 4, 606-611.

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