MOLECULAR DOKING AND ADMET STUDIES OF AMINO-PYRIMIDINE DERIVATIES AS MYCOBACTERIUM TUBERCULOSIS SER/THR PROTEIN KINASES B INHIBITORS
DOI:
https://doi.org/10.4314/jfas.v11i2.24Keywords:
Amino-pyrimidine, Tuberculosis, PknB, Molecular docking, ADMET.Abstract
We used the molecular docking method with Molegro software and we calculate ADME-T properties using Marvin Sketch and preADMET. The 29 amino-pyrimidines ligands were examined for docking studies with PknB (PDB Code: 2FUM).The Moldock score of the best three ligands L9, L12 and L21 are-161.475, -152.003 and-143.359 Kcal/Mol. These percentage shows that these candidature ligands have high binding energy percentage than the native MIX ligand. The ligand L21 has the human intestinal absorption (HIA), Caco-2 cell permeability, and plasma protein binding values of 85.48, 6.312 (nm/Sec.) and 93.097% respectively, which are comparable to MIX and the other ligands L9, L12. This computational study helped to prove that the ligand L21 have the ability to kill the Mycobacterium tuberculosis by inhibiting the expression of protein kinase B.
Downloads
Download data is not yet available.
References
[1] McDonough K A, Kress Y, Bloom B R, Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages. Infect Immun., 1993, 61 (7), 2763–2773.
[2] Rohini K , Srikumar P S, Insights from the docking and molecular dynamicssimulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis, Bioinformation, 2013, 9 (13), 685–689. doi: 10.6026/97320630009685
[3] Lougheed K E A, Osborne S A, Saxty B,Whalley D, Chapman TM, Bouloc N, Chugh J, Nott T J, Patel D, Spivey V L, Kettleborough C A, Bryans J S,Taylor D L, Smerdon S J and Buxton R S. Effective inhibitors of the essential kinase PknB and their potential as anti-mycobacterial agents. Tuberculosis (Edinb), 2011, 91 (4), 277–286.doi: 10.1016/j.tube.2011.03.005
[4] Gorakh W J , Sachan S, Ahuja D, and Angshu B . Designing of potential drug-like inhibitors to serine-threonine protein kinase b (pknb) in tuberculosis through computer-aided drug design World. J. Pharm. Res., 2014,3(2),3945-3974.
[5] Khamouli S , Belaidi S, Belaidi H, Belkhiri L , QSAR Studies of amino-pyrimidine derivatives as Mycobacterium tuberculosis Protein Kinase B inhibitors .Turkish Comp .Theo .Chem. (TC&TC)., 2018,2(2), 16 – 27. doi: 10.33435/tcandtc.397449
[6] Barthe P, Mukamolova G V, Roumestand C, and Cohen-Gonsaud M.The Structure of PknB Extracellular PASTA Domain from Mycobacterium tuberculosis Suggests a Ligand-Dependent Kinase Activation. Structure, 2010, 18 (5), 606–615. doi.org/10.1016/j.str.2010.02.013
[7] Young T A , Delagoutte B, Endrizzi J A, Falick A M, and Alber T.Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat. Struct. Biol., 2003,105(3), 168–174. doi:10.1038/nsb897
[8] Av-GayY, Jamil S, and Drews S J. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Infect. Immun., 1999, 67, (11), 5676–5682.
[9] Fernandez P et al..The Ser/Thr Protein Kinase PknB Is Essential for Sustaining Mycobacterial Growth. J. Bacteriol., 2006,188( 22), 7778–7784. doi: 10.1128/JB.00963-06
[10] Mieczkowski C, Iavarone AT, and Alber T. Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase. EMBO J., 2008, 27(23), 3186–3197. doi: 10.1038/emboj.2008.236.
[11] Sharma K, Gupta M, Krupa A, Srinivasan N, and Singh Y. EmbR a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium . FEBS J., 2006, 273 (12), 2711–2721. doi.org/10.1111/j.1742-4658.2006.05289.x
[12] Dasgupta A, Datta P, Kundu M, and Basu J. The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division.Microbiology,2006,152,493-504doi:10.1099/mic.0.28630-0.
[13] Kang CM, Abbott D W, Park S T, Dascher C C, Cantley L C, and Husson R N. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev., 2005, 19(14), 1692–1704.
doi :10.1101/gad.1311105
[14] Ortiz-Lombardía M, Pompeo F, Boitel B, and Alzari P M.Crystal structure of the catalytic domain of the PknB serine/threonine kinase from Mycobacterium tuberculosis. J. Biol. Chem., 2003, 278(15), pp. 13094–13100. doi:10.1074/jbc.M300660200
[15] Narayan A, Sachdeva P, Sharma K, Saini AK, Tyagi AK, and Singh Y. Serine threonine protein kinases of mycobacterial genus: phylogeny to function. Physiol Genomics., 2007, 29 (1), 66–75. doi :10.1152/physiolgenomics.00221.2006
[16] Villarino A et al.Proteomic identification of M. tuberculosis protein kinase substrates: PknB recruits GarA, a FHA domain-containing protein, through activation loop-mediated interactions. J. Mol. Biol., 2005, 350(5), 953–963. doi:10.1016/j.jmb.2005.05.049
[17] Chapman T M, Bouloc N, Buxton R S, Chugh J, Lougheed K E A, Osborne S A, Saxty B, Smerdon S J,Taylor D L and Whalley D. Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis, Bioorg .Med .Chem. Lett.,2012, 22 (9), 3349–3353.doi: 10.1016/j.bmcl.2012.02.107
[18] Seal A, Yogeeswari P, Sriram D, Consortium O, and Wild D J. Enhanced ranking of PknB Inhibitors using data fusion methods. Journal of Cheminformatics, 2013, 5 (1), 1-11. Jan. 2013. doi:10.1186/1758-2946-5-2
[19] Székely R et al. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Immunol. Lett., 2008,116 (2), 225–231. doi.org/10.1016/j.imlet.2007.12.005
[20] Hegymegi-Barakonyi B et al. Signalling inhibitors against Mycobacterium tuberculosis--early days of a new therapeutic concept in tuberculosis. Curr. Med. Chem., 2008,15 (26), 2760–2770.
[21] Wehenkel A et al. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Lett., 2006,580(13),3018–3022.doi: 10.1016/j.febslet.2006.04.046
[22] Khamouli S, Belaidi S, Almi Z, Medjahed S, and Belaidi H. Property/Activity Relationships and Drug Likeness for Pyrimidine Derivatives as Serine/Threonine Protein Kinase B Inhibitors. J. Bionanosci., 2017,11(4),301–309. doi.org/10.1166/jbns.2017.1445.
[23] Lyskov S and Gray J J. The Rosetta Dock server for local protein–protein docking. Nucleic Acids Res., 2008, 36(2), 233–238. doi:10.1093/nar/gkn216
[24] Ouassaf M,Belaidi S, Lotfy K, Daoud I, and Belaidi H.Molecular Docking Studies and ADMET Properties of New 1.2.3 Triazole Derivatives for Anti-Breast Cancer Activity.J. Bionanosci., 2018, 12,1-11. doi:10.1166/jbns.2018.1505
[25] 2FUM: 3-dimensional structure downloaded from http://www.rcsb.org/pdb.
[26] Wehenkel A et al.The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Lett., 2006,580(13), 3018–3022. doi:10.1016/j.febslet.2006.04.046.
[27] Ramachandran G N, Ramakrishnan C, and Sasisekharan V . Stereochemistry of polypeptide chain configurations. J. Mol. Biol., 1963,7, 95–99.
[28] Damre M V , Gangwal R P, Dhoke G V, Lalit M, Sharma D, Khandelwal K, and Sangamwar A T. 3D-QSAR and molecular docking studies of amino-pyrimidine derivatives as PknB inhibitors. J. Taiwan Inst. Chem. Eng., 2014, 45 (2), 354–364 doi.org/10.1016/j.jtice.2013.05.016
[29] Hyper Chem (Molecular Modeling System) Hypercube, Inc., 1115 NW, 4th Street, Gainesville, FL 32601, USA.2008.
[30] MarvinSketch 17.1.2, Chemaxon .2017, (http://www.chemaxon.com).
[31] http://molegro.com/mvd-product.php
[32] Bursulaya B D, Totrov M, Abagyan R, and Brooks C L .Comparative study of several algorithms for flexible ligand docking. J. Comput. Aided Mol. Des., 2003, 17(11), 755–763
[33] Thomsen R , Christensen M H. MolDock: A New Technique for High-Accuracy Molecular Docking. J. Med. Chem., 2006, 49 (11), 3315–3321. doi:10.1021/jm051197e
[34] Anuf A R, Ramaraj K. Inhibition of FGFR2 signal transduction in Acne Vulgaris using Bioactive Flavonoids: An Insilico approach . J .Med. Pharm. Sci., 2014, 2(2), 136–142.
[35] Wallace A C, Laskowski R A, and Thornton J M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 1995, 8(2), 127–134
[36] Veber D F, Johnson S R, Cheng H Y, Smith B R, Ward KW,and Kopple K D, Molecular properties that influence the oral bioavailability of drug candidates.J. Med. Chem., 2002 45(12), 2615-2623.
[37] Lipinski C A, Lombardo F, Dominy B W, and Feeney P J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. J. Adv.Drug Deliv. Rev., 2001, 46(1-3),3-26.
[38] Ajay A , Walters W P, and Murcko M A. Can We Learn To Distinguish between ‘Drug-like’ and ‘Nondrug-like’ Molecules?. J. Med. Chem., 1998,41 (18), 3314–3324. doi :10.1021/jm970666c
[39] Oprea T I, Allu T K, Fara D C, Rad R F,Ostopovici L, and Bologa C G . Lead-like, Drug-like or ‘Pub-like’: How different are they?. J Comput Aided Mol Des.,2007, 21(1–3), 113–119. doi:10.1007/s10822-007-9105-3
[40] Wagener M ,Van Geerestein V J .Potential Drugs and Nondrugs: Prediction and Identification of Important Structural Features . J. Chem. Inf. Comput. Sci., 2000, 40(2), 280–292. doi: 10.1021/ci990266t
[41] Kulkarni A, Han Y, and Hopfinger A J. Predicting Caco-2 Cell Permeation Coefficients of Organic Molecules Using Membrane-Interaction QSAR Analysis. J. Chem. Inf. Comput. Sci., 2002, 42(2), 331–342. doi: 10.1021/ci010108d
[42] Irvine J D et al. MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J Pharm Sci, vol. 88, no. 1, pp. 28–33, Jan. 1999.
doi:10.1021/js9803205
[43] Lovell S C et al. Structure validation by Calpha geometry: phi,psi and Cbeta deviation.Proteins, 2003,50(3), 437–450.
[44] Imberty A, Hardman K D, Carver J P, and Pérez S. Molecular modeling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology, 1991,1(6), 631–642.
[45] Sinko P J. Martin’s Physical Pharmacy and Pharmaceutical Sciences: Physical Chemical and Biopharmaceutical Principles in the Pharmaceutical Sciences, 6th Edition, Lippincott.2010, pp 183.
[46] Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth. Pharm. Res., 1997, vol. 14( 6), 763–766.
[47] Yazdanian M, Glynn S L,Wright J L, and Hawi A. Correlating partitioning and caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharm. Res., 1998, 15 (9),1490–1494.
[48] Schinkel A H. P-Glycoprotein, a gatekeeper in the blood-brain barrier.Adv. Drug Deliv. Rev.,1999, 36 (2–3), 179–194, Apr. 1999.
[2] Rohini K , Srikumar P S, Insights from the docking and molecular dynamicssimulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis, Bioinformation, 2013, 9 (13), 685–689. doi: 10.6026/97320630009685
[3] Lougheed K E A, Osborne S A, Saxty B,Whalley D, Chapman TM, Bouloc N, Chugh J, Nott T J, Patel D, Spivey V L, Kettleborough C A, Bryans J S,Taylor D L, Smerdon S J and Buxton R S. Effective inhibitors of the essential kinase PknB and their potential as anti-mycobacterial agents. Tuberculosis (Edinb), 2011, 91 (4), 277–286.doi: 10.1016/j.tube.2011.03.005
[4] Gorakh W J , Sachan S, Ahuja D, and Angshu B . Designing of potential drug-like inhibitors to serine-threonine protein kinase b (pknb) in tuberculosis through computer-aided drug design World. J. Pharm. Res., 2014,3(2),3945-3974.
[5] Khamouli S , Belaidi S, Belaidi H, Belkhiri L , QSAR Studies of amino-pyrimidine derivatives as Mycobacterium tuberculosis Protein Kinase B inhibitors .Turkish Comp .Theo .Chem. (TC&TC)., 2018,2(2), 16 – 27. doi: 10.33435/tcandtc.397449
[6] Barthe P, Mukamolova G V, Roumestand C, and Cohen-Gonsaud M.The Structure of PknB Extracellular PASTA Domain from Mycobacterium tuberculosis Suggests a Ligand-Dependent Kinase Activation. Structure, 2010, 18 (5), 606–615. doi.org/10.1016/j.str.2010.02.013
[7] Young T A , Delagoutte B, Endrizzi J A, Falick A M, and Alber T.Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat. Struct. Biol., 2003,105(3), 168–174. doi:10.1038/nsb897
[8] Av-GayY, Jamil S, and Drews S J. Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB. Infect. Immun., 1999, 67, (11), 5676–5682.
[9] Fernandez P et al..The Ser/Thr Protein Kinase PknB Is Essential for Sustaining Mycobacterial Growth. J. Bacteriol., 2006,188( 22), 7778–7784. doi: 10.1128/JB.00963-06
[10] Mieczkowski C, Iavarone AT, and Alber T. Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase. EMBO J., 2008, 27(23), 3186–3197. doi: 10.1038/emboj.2008.236.
[11] Sharma K, Gupta M, Krupa A, Srinivasan N, and Singh Y. EmbR a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium . FEBS J., 2006, 273 (12), 2711–2721. doi.org/10.1111/j.1742-4658.2006.05289.x
[12] Dasgupta A, Datta P, Kundu M, and Basu J. The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division.Microbiology,2006,152,493-504doi:10.1099/mic.0.28630-0.
[13] Kang CM, Abbott D W, Park S T, Dascher C C, Cantley L C, and Husson R N. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape. Genes Dev., 2005, 19(14), 1692–1704.
doi :10.1101/gad.1311105
[14] Ortiz-Lombardía M, Pompeo F, Boitel B, and Alzari P M.Crystal structure of the catalytic domain of the PknB serine/threonine kinase from Mycobacterium tuberculosis. J. Biol. Chem., 2003, 278(15), pp. 13094–13100. doi:10.1074/jbc.M300660200
[15] Narayan A, Sachdeva P, Sharma K, Saini AK, Tyagi AK, and Singh Y. Serine threonine protein kinases of mycobacterial genus: phylogeny to function. Physiol Genomics., 2007, 29 (1), 66–75. doi :10.1152/physiolgenomics.00221.2006
[16] Villarino A et al.Proteomic identification of M. tuberculosis protein kinase substrates: PknB recruits GarA, a FHA domain-containing protein, through activation loop-mediated interactions. J. Mol. Biol., 2005, 350(5), 953–963. doi:10.1016/j.jmb.2005.05.049
[17] Chapman T M, Bouloc N, Buxton R S, Chugh J, Lougheed K E A, Osborne S A, Saxty B, Smerdon S J,Taylor D L and Whalley D. Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis, Bioorg .Med .Chem. Lett.,2012, 22 (9), 3349–3353.doi: 10.1016/j.bmcl.2012.02.107
[18] Seal A, Yogeeswari P, Sriram D, Consortium O, and Wild D J. Enhanced ranking of PknB Inhibitors using data fusion methods. Journal of Cheminformatics, 2013, 5 (1), 1-11. Jan. 2013. doi:10.1186/1758-2946-5-2
[19] Székely R et al. A novel drug discovery concept for tuberculosis: inhibition of bacterial and host cell signalling. Immunol. Lett., 2008,116 (2), 225–231. doi.org/10.1016/j.imlet.2007.12.005
[20] Hegymegi-Barakonyi B et al. Signalling inhibitors against Mycobacterium tuberculosis--early days of a new therapeutic concept in tuberculosis. Curr. Med. Chem., 2008,15 (26), 2760–2770.
[21] Wehenkel A et al. The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Lett., 2006,580(13),3018–3022.doi: 10.1016/j.febslet.2006.04.046
[22] Khamouli S, Belaidi S, Almi Z, Medjahed S, and Belaidi H. Property/Activity Relationships and Drug Likeness for Pyrimidine Derivatives as Serine/Threonine Protein Kinase B Inhibitors. J. Bionanosci., 2017,11(4),301–309. doi.org/10.1166/jbns.2017.1445.
[23] Lyskov S and Gray J J. The Rosetta Dock server for local protein–protein docking. Nucleic Acids Res., 2008, 36(2), 233–238. doi:10.1093/nar/gkn216
[24] Ouassaf M,Belaidi S, Lotfy K, Daoud I, and Belaidi H.Molecular Docking Studies and ADMET Properties of New 1.2.3 Triazole Derivatives for Anti-Breast Cancer Activity.J. Bionanosci., 2018, 12,1-11. doi:10.1166/jbns.2018.1505
[25] 2FUM: 3-dimensional structure downloaded from http://www.rcsb.org/pdb.
[26] Wehenkel A et al.The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria. FEBS Lett., 2006,580(13), 3018–3022. doi:10.1016/j.febslet.2006.04.046.
[27] Ramachandran G N, Ramakrishnan C, and Sasisekharan V . Stereochemistry of polypeptide chain configurations. J. Mol. Biol., 1963,7, 95–99.
[28] Damre M V , Gangwal R P, Dhoke G V, Lalit M, Sharma D, Khandelwal K, and Sangamwar A T. 3D-QSAR and molecular docking studies of amino-pyrimidine derivatives as PknB inhibitors. J. Taiwan Inst. Chem. Eng., 2014, 45 (2), 354–364 doi.org/10.1016/j.jtice.2013.05.016
[29] Hyper Chem (Molecular Modeling System) Hypercube, Inc., 1115 NW, 4th Street, Gainesville, FL 32601, USA.2008.
[30] MarvinSketch 17.1.2, Chemaxon .2017, (http://www.chemaxon.com).
[31] http://molegro.com/mvd-product.php
[32] Bursulaya B D, Totrov M, Abagyan R, and Brooks C L .Comparative study of several algorithms for flexible ligand docking. J. Comput. Aided Mol. Des., 2003, 17(11), 755–763
[33] Thomsen R , Christensen M H. MolDock: A New Technique for High-Accuracy Molecular Docking. J. Med. Chem., 2006, 49 (11), 3315–3321. doi:10.1021/jm051197e
[34] Anuf A R, Ramaraj K. Inhibition of FGFR2 signal transduction in Acne Vulgaris using Bioactive Flavonoids: An Insilico approach . J .Med. Pharm. Sci., 2014, 2(2), 136–142.
[35] Wallace A C, Laskowski R A, and Thornton J M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 1995, 8(2), 127–134
[36] Veber D F, Johnson S R, Cheng H Y, Smith B R, Ward KW,and Kopple K D, Molecular properties that influence the oral bioavailability of drug candidates.J. Med. Chem., 2002 45(12), 2615-2623.
[37] Lipinski C A, Lombardo F, Dominy B W, and Feeney P J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. J. Adv.Drug Deliv. Rev., 2001, 46(1-3),3-26.
[38] Ajay A , Walters W P, and Murcko M A. Can We Learn To Distinguish between ‘Drug-like’ and ‘Nondrug-like’ Molecules?. J. Med. Chem., 1998,41 (18), 3314–3324. doi :10.1021/jm970666c
[39] Oprea T I, Allu T K, Fara D C, Rad R F,Ostopovici L, and Bologa C G . Lead-like, Drug-like or ‘Pub-like’: How different are they?. J Comput Aided Mol Des.,2007, 21(1–3), 113–119. doi:10.1007/s10822-007-9105-3
[40] Wagener M ,Van Geerestein V J .Potential Drugs and Nondrugs: Prediction and Identification of Important Structural Features . J. Chem. Inf. Comput. Sci., 2000, 40(2), 280–292. doi: 10.1021/ci990266t
[41] Kulkarni A, Han Y, and Hopfinger A J. Predicting Caco-2 Cell Permeation Coefficients of Organic Molecules Using Membrane-Interaction QSAR Analysis. J. Chem. Inf. Comput. Sci., 2002, 42(2), 331–342. doi: 10.1021/ci010108d
[42] Irvine J D et al. MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J Pharm Sci, vol. 88, no. 1, pp. 28–33, Jan. 1999.
doi:10.1021/js9803205
[43] Lovell S C et al. Structure validation by Calpha geometry: phi,psi and Cbeta deviation.Proteins, 2003,50(3), 437–450.
[44] Imberty A, Hardman K D, Carver J P, and Pérez S. Molecular modeling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology, 1991,1(6), 631–642.
[45] Sinko P J. Martin’s Physical Pharmacy and Pharmaceutical Sciences: Physical Chemical and Biopharmaceutical Principles in the Pharmaceutical Sciences, 6th Edition, Lippincott.2010, pp 183.
[46] Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth. Pharm. Res., 1997, vol. 14( 6), 763–766.
[47] Yazdanian M, Glynn S L,Wright J L, and Hawi A. Correlating partitioning and caco-2 cell permeability of structurally diverse small molecular weight compounds. Pharm. Res., 1998, 15 (9),1490–1494.
[48] Schinkel A H. P-Glycoprotein, a gatekeeper in the blood-brain barrier.Adv. Drug Deliv. Rev.,1999, 36 (2–3), 179–194, Apr. 1999.
Downloads
Published
2019-04-29
How to Cite
KHAMOULI, S.; BELAIDI, S.; LANEZ, T. MOLECULAR DOKING AND ADMET STUDIES OF AMINO-PYRIMIDINE DERIVATIES AS MYCOBACTERIUM TUBERCULOSIS SER/THR PROTEIN KINASES B INHIBITORS. Journal of Fundamental and Applied Sciences, [S. l.], v. 11, n. 2, p. 914–939, 2019. DOI: 10.4314/jfas.v11i2.24. Disponível em: https://jfas.info/index.php/JFAS/article/view/429. Acesso em: 30 jan. 2025.
Issue
Section
Articles
Submissions
