Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis, Molecular Docking and Molecular Dynamics Simulation of 2- Thioxothiazolidin-4-One Derivatives against Gp41

Author(s): Nahid Tamiz, Tahereh Mostashari-Rad, Aylar Najafipour, Sandra Claes, Dominique Schols and Afshin Fassihi*

Volume 19, Issue 1, 2021

Published on: 03 September, 2020

Page: [47 - 60] Pages: 14

DOI: 10.2174/1570162X18666200903172127

Price: $65

Abstract

Introduction: Gp41 and its conserved hydrophobic groove on the N-terminal heptad repeat region are attractive targets in the design of HIV-1 entry inhibitors. Linearly extended molecules have shown potent anti-HIV-1 activity for their effective interactions with the gp41 binding pocket. Rhodanine ring attached to substituted pyrrole or furan rings has been proved a preferred moiety to be inserted inside the molecular structure of the gp41 inhibitors.

Objectives: Based on the previous findings we are going to describe some rhodanine derivatives in which a substituted imidazole ring is introduced in place of the pyrrole or furan rings. The compounds’ flexibility is increased by inserting methylene groups inside the main scaffold.

Methods: Molecular docking and molecular dynamics simulations approaches were exploited to investigate the chemical interactions and the stability of the designed ligands-gp41 complex. All compounds were synthesized and their chemical structures were elucidated by 1HNMR, 13CNMR, FTIR and Mass spectroscopy. Biological activities of the compounds against HIV-1 and HIV-2 and their cellular toxicities against the T-lymphocyte (MT-4) cell line were determined.

Results: All the designed compounds showed proper and stable chemical interactions with gp41 according to the in silico studies. The results of the biological tests proved none of the compounds active against HIV-1 replication in cell cultures.

Conclusion: Since all the studied compounds were potently toxic for the host cell; it was therefore not possible to assess their anti-HIV activities.

Keywords: 2-thioxothiazolidin-4-one, molecular docking, molecular dynamics simulation, anti-HIV, gp41, synthesis.

« Previous Next »
Graphical Abstract

[1]
Rey FA, Lok SM. Lok S. M, common features of enveloped viruses and implications for immunogen design for next-generation vaccines. Cell 2018; 172(6): 1319-34.
[http://dx.doi.org/10.1016/j.cell.2018.02.054] [PMID: 29522750]
[2]
White JM, Whittaker GR. Fusion of Enveloped Viruses in Endosomes. Traffic 2016; 17(6): 593-614.
[http://dx.doi.org/10.1111/tra.12389] [PMID: 26935856]
[3]
Weissenhorn W, Dessen A, Calder LJ, Harrison SC, Skehel JJ, Wiley DC. Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol 1999; 16(1): 3-9.
[http://dx.doi.org/10.1080/096876899294706] [PMID: 10332732]
[4]
Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell 1997; 89(2): 263-73.
[http://dx.doi.org/10.1016/S0092-8674(00)80205-6] [PMID: 9108481]
[5]
Tran EEH, Borgnia MJ, Kuybeda O, et al. Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog 2012; 8(7): e1002797.
[http://dx.doi.org/10.1371/journal.ppat.1002797] [PMID: 22807678]
[6]
Lu L, Yu F, Cai L, Debnath AK, Jiang S. Development of small-molecule HIV entry inhibitors specifically targeting gp120 or gp41. Curr Top Med Chem 2016; 16(10): 1074-90.
[http://dx.doi.org/10.2174/1568026615666150901114527] [PMID: 26324044]
[7]
Wang Q, Finzi A, Sodroski J. The conformational states of the HIV-1 envelope glycoproteins TRENDS MICROBIOL. 2020.
[8]
Marin M, Kushnareva Y, Mason CS, Chanda SK, Melikyan GB. HIV-1 fusion with CD4+ T cells is promoted by proteins involved in endocytosis and intracellular membrane trafficking. Viruses 2019; 11(2): 100-16.
[http://dx.doi.org/10.3390/v11020100] [PMID: 30691001]
[9]
Klug YA, Schwarzer R, Rotem E, et al. The HIV gp41 fusion protein inhibits T cell activation through the lentiviral lytic peptide 2 motif. Biochemistry 2019; 58(6): 818-32.
[http://dx.doi.org/10.1021/acs.biochem.8b01175] [PMID: 30602116]
[10]
Suttisintong K, Kaewchangwat N, Thanayupong E, Nerungsi C, Srikun O, Pungpo P. Recent progress in the development of HIV-1 entry inhibitors: from small molecules to potent anti-HIV agents. Curr Top Med Chem 2019; 19(18): 1599-620.
[http://dx.doi.org/10.2174/1568026619666190712204050] [PMID: 31424370]
[11]
Chen B. molecular mechanism of HIV-1 entry. Trends Microbiol 2019; 27(10): 878-91.
[http://dx.doi.org/10.1016/j.tim.2019.06.002] [PMID: 31262533]
[12]
Kangueane P. HIV-1 GP160 (GP120/GP40) trimer ENV spike protein. Bioinformation Discovery. Cham: Springer 2018.
[http://dx.doi.org/10.1007/978-3-319-95327-4_9]
[13]
Puhl AC, Garzino Demo A, Makarov VA, Ekins S. New targets for HIV drug discovery. Drug Discov Today 2019; 24(5): 1139-47.
[http://dx.doi.org/10.1016/j.drudis.2019.03.013] [PMID: 30885676]
[14]
Yi HA, Fochtman BC, Rizzo RC, Jacobs A. Inhibition of HIV Entry by Targeting the Envelope Transmembrane Subunit gp41. Curr HIV Res 2016; 14(3): 283-94.
[http://dx.doi.org/10.2174/1570162X14999160224103908] [PMID: 26957202]
[15]
Wang H, Barnes O C, Yang Z, et al. Partially open HIV-1 envelope structures exhibit conformational changes relevant for coreceptor binding and fusion. 2018; 24: 579-92.
[http://dx.doi.org/10.1016/j.chom.2018.09.003]
[16]
Zhuang M, Vassell R, Yuan C, et al. Mutations that increase the stability of the postfusion gp41 conformation of the HIV-1 envelope glycoprotein are selected by both an X4 and R5 HIV-1 virus to escape fusion inhibitors corresponding to heptad repeat 1 of gp41, but the gp120 adaptive mutations differ between the two viruses. J Virol 2019; 93(11): e00142-19.
[http://dx.doi.org/10.1128/JVI.00142-19] [PMID: 30894471]
[17]
Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387(6631): 426-30.
[http://dx.doi.org/10.1038/387426a0] [PMID: 9163431]
[18]
Buzon V, Natrajan G, Schibli D, Campelo F, Kozlov MM, Weissenhorn W. Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions. PLoS Pathog 2010; 6(5): e1000880.
[http://dx.doi.org/10.1371/journal.ppat.1000880] [PMID: 20463810]
[19]
Liu D, Wang H, Yamamoto M, et al. Six-helix bundle completion in the distal C-terminal heptad repeat region of gp41 is required for efficient human immunodeficiency virus type 1 infection. Retrovirology 2018; 15(1): 27.
[http://dx.doi.org/10.1186/s12977-018-0410-9] [PMID: 29609648]
[20]
Su S, Wang Q, Xu W, et al. A novel HIV-1 gp41 tripartite model for rational design of HIV-1 fusion inhibitors with improved antiviral activity. AIDS 2017; 31(7): 885-94.
[http://dx.doi.org/10.1097/QAD.0000000000001415] [PMID: 28121713]
[21]
Aisenbrey C, Bechinger B. Structure, interactions and membrane topology of HIV gp41 ectodomain sequences. Biochim Biophys Acta Biomembr 2020; 1862(7): 183274-305.
[http://dx.doi.org/10.1016/j.bbamem.2020.183274] [PMID: 32197992]
[22]
Lin M, Da LT. Refolding dynamics of gp41 from pre-fusion to pre-hairpin states during HIV-1 Entry. J Chem Inf Model 2020; 60(1): 162-74.
[http://dx.doi.org/10.1021/acs.jcim.9b00746] [PMID: 31845803]
[23]
Wang Q, Su S, Xue J, et al. An amphipathic peptide targeting the gp41 cytoplasmic tail kills HIV-1 virions and infected cells. Sci Transl Med 2020; 12(546): eaaz2254.
[http://dx.doi.org/10.1126/scitranslmed.aaz2254] [PMID: 32493792]
[24]
Leslie GJ, Wang J, Richardson MW, et al. Potent and broad inhibition of HIV-1 by a peptide from the gp41 heptad repeat-2 domain conjugated to the CXCR4 amino terminus. PLoS Pathog 2016; 12(11): e1005983.
[http://dx.doi.org/10.1371/journal.ppat.1005983] [PMID: 27855210]
[25]
Qi Q, Wang Q, Chen W, et al. HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions. Emerg Microbes Infect 2017; 6(6): e59.
[http://dx.doi.org/10.1038/emi.2017.46] [PMID: 28634358]
[26]
Zhang X, Zhu Y, Hu H, et al. Structural insights into the mechanisms of action of short-peptide HIV-1 fusion inhibitors targeting the Gp41 pocket. Front Cell Infect Microbiol 2018; 8: 51.
[http://dx.doi.org/10.3389/fcimb.2018.00051] [PMID: 29535974]
[27]
Kilby JM, Lalezari JP, Eron JJ, et al. Antiviral Activity of Subcutaneous Enfuvirtide (T-20), a Peptide Inhibitor of gp41-Mediated Virus Fusion, in HIV-Infected Adults. AIDS RES. HUM. RETROV 2002; 18: 685-93.
[PMID: 12167274]
[28]
Cervia JS, Smith MA, Smith AM. Enfuvirtide (T-20): a novel human immunodeficiency virus type 1 fusion inhibitor. Clin Infect Dis 2003; 37(8): 1102-6.
[http://dx.doi.org/10.1086/378302] [PMID: 14523775]
[29]
Liu S, Wu S, Jiang S. HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds. Curr Pharm Des 2007; 13(2): 143-62.
[http://dx.doi.org/10.2174/138161207779313722] [PMID: 17269924]
[30]
LaBonte J, Lebbos J, Kirkpatrick P. Enfuvirtide. Nat Rev Drug Discov 2003; 2(5): 345-6.
[http://dx.doi.org/10.1038/nrd1091] [PMID: 12755128]
[31]
Manfredi R, Sabbatani S. A novel antiretroviral class (fusion inhibitors) in the management of HIV infection. Present features and future perspectives of enfuvirtide (T-20). Curr Med Chem 2006; 13(20): 2369-84.
[http://dx.doi.org/10.2174/092986706777935069] [PMID: 16918361]
[32]
Zhang DW, Luo RH, Xu L, et al. A HTRF based competitive binding assay for screening specific inhibitors of HIV-1 capsid assembly targeting the C-Terminal domain of capsid. Antiviral Res 2019; 169: 104544-53.
[http://dx.doi.org/10.1016/j.antiviral.2019.104544] [PMID: 31254557]
[33]
Foy K, Juethner SN. Enfuvirtide (T-20): potentials and challenges. J Assoc Nurses AIDS Care 2004; 15(6): 65-71.
[http://dx.doi.org/10.1177/1055329003256414] [PMID: 15538017]
[34]
Mostashari Rad T, Saghaie L, Fassihi A. HIV-1 entry inhibitors: A review of experimental and computational studies. Chem Biodivers 2018; 15(10): e1800159.
[http://dx.doi.org/10.1002/cbdv.201800159] [PMID: 30027572]
[35]
Jiang S, Lu H, Liu S, Zhao Q, He Y, Debnath AK. N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion. Antimicrob Agents Chemother 2004; 48(11): 4349-59.
[http://dx.doi.org/10.1128/AAC.48.11.4349-4359.2004] [PMID: 15504864]
[36]
Liu K, Lu H, Hou L, et al. Design, synthesis, and biological evaluation of N-carboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41. J Med Chem 2008; 51(24): 7843-54.
[http://dx.doi.org/10.1021/jm800869t] [PMID: 19053778]
[37]
Zhou G, Wu D, Hermel E, Balogh E, Gochin M. Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41. Bioorg Med Chem Lett 2010; 20(5): 1500-3.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.111] [PMID: 20153190]
[38]
Zhou G, Wu D, Snyder B, Ptak RG, Kaur H, Gochin M. Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41. J Med Chem 2011; 54(20): 7220-31.
[http://dx.doi.org/10.1021/jm200791z] [PMID: 21928824]
[39]
Zhou G, Sofiyev V, Kaur H, et al. Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41. J Med Chem 2014; 57(12): 5270-81.
[http://dx.doi.org/10.1021/jm500344y] [PMID: 24856833]
[40]
He XY, Zou P, Qiu J, et al. Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors. Bioorg Med Chem 2011; 19(22): 6726-34.
[http://dx.doi.org/10.1016/j.bmc.2011.09.047] [PMID: 22014749]
[41]
He XY, Lu L, Qiu J, et al. Small molecule fusion inhibitors: design, synthesis and biological evaluation of (Z)-3-(5-(3-benzyl-4-oxo-2-thioxothiazolidinylidene)methyl)-N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrroles and related derivatives targeting HIV-1 gp41. Bioorg Med Chem 2013; 21(23): 7539-48.
[http://dx.doi.org/10.1016/j.bmc.2013.04.046] [PMID: 23673219]
[42]
Jiang S, Tala SR, Lu H, et al. Design, synthesis, and biological activity of novel 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1 fusion inhibitors targeting gp41. J Med Chem 2011; 54(2): 572-9.
[http://dx.doi.org/10.1021/jm101014v] [PMID: 21190369]
[43]
Qiu J, Liang T, Wu J, et al. N-Substituted pyrrole derivative 12m inhibits HIV-1 entry by targeting Gp41 of HIV-1 envelope glycoprotein. Front Pharmacol 2019; 10: 859-71.
[http://dx.doi.org/10.3389/fphar.2019.00859] [PMID: 31427969]
[44]
Sepehri S, Soleymani S, Zabihollahi R, et al. Design, synthesis, and anti‐HIV‐1 evaluation of a novel series of 1,2,3,4‐tetrahydropyrimidine‐5‐carboxylic acid derivatives. Chem Biodivers 2018; 15(4): e1700502.
[http://dx.doi.org/10.1002/cbdv.201700502] [PMID: 29411517]
[45]
Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009; 30(16): 2785-91.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[46]
HyperChem. Release 8.0 for Windows, Molecular Modeling System: HyperCube 2007.
[47]
Gasteiger J, Marsili M. Iterative partial equalization of orbital electronegativity - a rapid access to atomic charges. Tetrahedron 1980; 22: 3219-28.
[http://dx.doi.org/10.1016/0040-4020(80)80168-2]
[48]
DSVisualizer, Accelrys Software Inc. San Diego CA USA. 2014.
[49]
Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. J Comput Chem 2005; 26(16): 1701-18.
[http://dx.doi.org/10.1002/jcc.20291] [PMID: 16211538]
[50]
Lemkul J. From proteins to perturbed hamiltonians: a suite of tutorials for the GROMACS-2018 molecular simulation package. Liv J Comput Mol Sci 2018; 1: 5068.
[51]
Schüttelkopf AW, van Aalten DM. PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr 2004; 60(Pt 8): 1355-63.
[http://dx.doi.org/10.1107/S0907444904011679] [PMID: 15272157]
[52]
Hess B, Bekker H, Brendsen JCH, et al. LINCS: linear constraint solver for molecular simulations. J Comput Chem 1997; 18: 1463-72.
[http://dx.doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H]
[53]
Darden t,York D, Pedersen L. Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. J Chem Phys 1993; 98: 10089-92.
[http://dx.doi.org/10.1063/1.464397]
[54]
Mostashari-Rad T, Saghaei L, Fassihi A. Gp41 inhibitory activity prediction of theaflavin derivatives using ligand/structure-based virtual screening approaches. Comput Biol Chem 2019; 79: 119-26.
[http://dx.doi.org/10.1016/j.compbiolchem.2019.02.001] [PMID: 30785021]
[55]
Swain SS, Paidesetty SK, Dehury B, Das M, Vedithi SC, Padhy RN. Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae. Sci Rep 2020; 10(1): 6839-50.
[http://dx.doi.org/10.1038/s41598-020-63913-9] [PMID: 32322091]
[56]
Dahiya R, Mohammad T, Roy S, et al. Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: Towards implications in anticancer therapy. Int J Biol Macromol 2019; 136: 1076-85.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.06.158] [PMID: 31233792]
[57]
Gulzar M, Syed SB, Khan FI, et al. Elucidation of interaction mechanism of ellagic acid to the integrin linked kinase. Int J Biol Macromol 2019; 122: 1297-304.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.09.089] [PMID: 30227205]
[58]
Bhardwaj V, Purohit R. Computational investigation on effect of mutations in PCNA resulting in structural perturbations and inhibition of mismatch repair pathway. J Biomol Struct Dyn 2020; 38(7): 1963-74.
[http://dx.doi.org/10.1080/07391102.2019.1621210] [PMID: 31138032]
[59]
Vermeire K, Princen K, Hatse S, et al. CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro. AIDS 2004; 18(16): 2115-25.
[http://dx.doi.org/10.1097/00002030-200411050-00003] [PMID: 15577644]
[60]
Mostashari-Rad T, Arian R, Sadri H, et al. Study of CXCR4 chemokine receptor inhibitors using QSPR and molecular docking methodologies. J Theor Comput Chem 2019; 18: 1950018.
[http://dx.doi.org/10.1142/S0219633619500184]
[61]
Fayyazi N, Esmaeili S, Taheri S, et al. Pharmacophore modeling, synthesis, scaffold hopping and biological β- hematin inhibition interaction studies for anti-malaria compounds. Curr Top Med Chem 2019; 19(30): 2743-65.
[http://dx.doi.org/10.2174/1568026619666191116160326] [PMID: 31738136]
[62]
Fayyazi N, Fassihi A, Esmaeili S, Taheri S, Ghasemi JB, Saghaie L. Molecular dynamics simulation and 3D-pharmacophore analysis of new quinoline-based analogues with dual potential against EGFR and VEGFR-2. Int J Biol Macromol 2020; 142: 94-113.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.09.077] [PMID: 31521657]
[63]
Pradeepkiran JA, Reddy PH. Structure based design and molecular docking studies for phosphorylated tau inhibitors in alzheimer’s disease. Cells 2019; 8(3): 260-86.
[http://dx.doi.org/10.3390/cells8030260] [PMID: 30893872]
[64]
Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev 2017; 9(2): 91-102.
[http://dx.doi.org/10.1007/s12551-016-0247-1] [PMID: 28510083]
[65]
Tao X, Huang Y, Wang C, et al. Recent developments in molecular docking technology applied in food science: a review. I. Food Sci Technol 2019; 55: 33-45.
[66]
Vilar S, Sobarzo-Sánchez E, Uriarte E. In silico prediction of P-glycoprotein binding: Insights from molecular docking studies. Curr Med Chem 2019; 26(10): 1746-60.
[http://dx.doi.org/10.2174/0929867325666171129121924] [PMID: 29189117]
[67]
Alonso H, Bliznyuk AA, Gready JE. Combining docking and molecular dynamic simulations in drug design. Med Res Rev 2006; 26(5): 531-68.
[http://dx.doi.org/10.1002/med.20067] [PMID: 16758486]
[68]
Zhang J L, Zheng Q C, Chu W. Drug Design Benefits from Molecular Dynamics: Some Examples CURR COMPUT-AID DRUG 2013; 9: 532-46.
[69]
Pradiba D, Aarthy M, Shunmugapriya V, Singh SK, Vasanthi M. Structural insights into the binding mode of flavonols with the active site of matrix metalloproteinase-9 through molecular docking and molecular dynamic simulations studies. J Biomol Struct Dyn 2018; 36(14): 3718-39.
[http://dx.doi.org/10.1080/07391102.2017.1397058] [PMID: 29068268]
[70]
Mehranfar F, Bordbar A. A combined spectroscopic, molecular docking and molecular dynamic simulation study on the interaction of quercetin with β-casein nanoparticles J PHOTOCH PHOTOBIO B 2013; 127: 100-7.
[71]
Sixto-López Y, Bello M, Correa-Basurto J. Insights into structural features of HDAC1 and its selectivity inhibition elucidated by Molecular dynamic simulation and Molecular Docking. J Biomol Struct Dyn 2019; 37(3): 584-610.
[http://dx.doi.org/10.1080/07391102.2018.1441072] [PMID: 29447615]
[72]
Bandaru S, Alvala M, Nayarisseri A, et al. Molecular dynamic simulations reveal suboptimal binding of salbutamol in T164I variant of β2 adrenergic receptor. PLoS One 2017; 12(10): e0186666.
[http://dx.doi.org/10.1371/journal.pone.0186666] [PMID: 29053759]
[73]
Nukoolkarn V, Lee VS, Malaisree M, Aruksakulwong O, Hannongbua S. Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors. J Theor Biol 2008; 254(4): 861-7.
[http://dx.doi.org/10.1016/j.jtbi.2008.07.030] [PMID: 18706430]
[74]
Shafiee A, Mojarrad JS, Jalili MA, et al. Syntheses of substituted pyrrolo [2, 3‐d] imidazole‐5‐carboxylates and substitued pyrrolo [3, 2‐d] imidazole‐5‐carboxylates. J Heterocycl Chem 2002; 39: 367-73.
[http://dx.doi.org/10.1002/jhet.5570390221]
[75]
Katritzky AR, Tala SR, Lu H, et al. Design, synthesis, and structure-activity relationship of a novel series of 2-aryl 5-(4-oxo-3-phenethyl-2-thioxothiazolidinylidenemethyl)furans as HIV-1 entry inhibitors. J Med Chem 2009; 52(23): 7631-9.
[http://dx.doi.org/10.1021/jm900450n] [PMID: 19746983]
[76]
Martinez A, Alonso M, Castro A, et al. SAR and 3D-QSAR studies on thiadiazolidinone derivatives: exploration of structural requirements for glycogen synthase kinase 3 inhibitors. J Med Chem 2005; 48(23): 7103-12.
[http://dx.doi.org/10.1021/jm040895g] [PMID: 16279768]

Rights & Permissions Print Cite
Article Metrics
17
© 2024 Bentham Science Publishers | Privacy Policy