Computational discovery of sulfonamide derivatives as potential inhibitors of the cruzain enzyme from T. cruzi by molecular docking, molecular dynamics and MM/GBSA approaches

References

• Adasme MF, Bolz SN, Adelmann L, et al. Repositioned drugs for chagas disease unveiled via structure-based drug repositioning. Int J Mol Sci. 2020;21(22):8809. doi:10.3390/ijms21228809.
   PubMed Web of Science ®Google Scholar
• Martins-Melo FR, Castro MC, Werneck GL. Levels and trends in chagas disease-related mortality in Brazil, 2000–2019. Acta Trop. 2021;220:105948. doi:10.1016/j.actatropica.2021.105948.
   PubMed Web of Science ®Google Scholar
• Ferreira RAA, Pauli I, Sampaio TS, et al. Structure-based and molecular modeling studies for the discovery of cyclic imides as reversible cruzain inhibitors with potent anti-trypanosoma cruzi activity. Front Chem. 2019;7. doi:10.3389/fchem.2019.00798.
   Web of Science ®Google Scholar
• Ferreira AM, Sabino ÉC, Oliveira LCd, et al. Impact of the social context on the prognosis of Chagas disease patients: multilevel analysis of a Brazilian cohort. PLoS Negl Trop Dis. 2020;14(6):e0008399. doi:10.1371/journal.pntd.0008399.
   PubMed Web of Science ®Google Scholar
• Rodney Rodrigues de Assis D, Almeida Oliveira A, Luiz Porto S, et al. 4-Chlorophenylthioacetone-derived thiosemicarbazones as potent antitrypanosomal drug candidates: investigations on the mode of action. Bioorg Chem. 2021;113:105018. doi:10.1016/j.bioorg.2021.105018.
   PubMed Web of Science ®Google Scholar
• Molina I, Salvador F, Sánchez-Montalvá A, et al. Toxic profile of benznidazole in patients with chronic chagas disease: risk factors and comparison of the product from two different manufacturers. Antimicrob Agents Chemother. 2015;59(10):6125–6131. doi:10.1128/AAC.04660-14.
   PubMed Web of Science ®Google Scholar
• Martinez-Peinado N, Martori C, Cortes-Serra N, et al. Anti-Trypanosoma cruzi activity of metabolism modifier compounds. Int J Mol Sci. 2021;22(2):688. doi:10.3390/ijms22020688.
   PubMed Web of Science ®Google Scholar
• Sepúlveda-Robles O, Espinoza-Gutiérrez B, Gomez-Verjan JC, et al. Trypanocidal and toxicological assessment in vitro and in silico of three sesquiterpene lactones from Asteraceae plant species. Food Chem Toxicol. 2019;125:55–61. doi:10.1016/j.fct.2018.12.023.
   PubMed Web of Science ®Google Scholar
• Barbosa da Silva E, Dall E, Briza P, et al. Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design. Acta Crystallogr, Sect F: Struct Biol Cryst Commun. 2019;75(6):419–427. doi:10.1107/S2053230X19006320.
   Google Scholar
• Souza ALPF, Cardoso FJB, Martins LS, et al. Molecular modelling study of heteroarylamide/sulfonamide compounds with antitrypanosomal activity. J Braz Chem Soc. 2021;32(1):83–97. doi:10.21577/0103-5053.20200158.
   Web of Science ®Google Scholar
• Kumar Verma S, Verma R, Xue F, et al. Antibacterial activities of sulfonyl or sulfonamide containing heterocyclic derivatives and its structure-activity relationships (SAR) studies: a critical review. Bioorg Chem. 2020;105:104400. doi:10.1016/j.bioorg.2020.104400.
   PubMed Web of Science ®Google Scholar
• Othman IMM, Mahross MH, Gad-Elkareem MAM, et al. Toward a treatment of antibacterial and antifungal infections: design, synthesis and in vitro activity of novel arylhydrazothiazolylsulfonamides analogues and their insight of DFT, docking and molecular dynamic simulations. J Mol Struct. 2021;1243:130862. doi:10.1016/j.molstruc.2021.130862.
   Web of Science ®Google Scholar
• Papadopoulou MV, Bloomer WD, Rosenzweig HS, et al. Novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents. Eur J Med Chem. 2014;87:79–88. doi:10.1016/j.ejmech.2014.09.045.
   PubMed Web of Science ®Google Scholar
• Gurung AB, Ali MA, Lee J, et al. An updated review of computer-aided drug design and its application to COVID-19. Biomed Res Int. 2021;2021:1–18. doi:10.1155/2021/8853056.
   PubMed Web of Science ®Google Scholar
• Bryce RA. Physics-based scoring of protein–ligand interactions: explicit polarizability, quantum mechanics and free energies. Future Med Chem. 2011;3(6):683–698. doi:10.4155/fmc.11.30.
   PubMed Web of Science ®Google Scholar
• Batool M, Ahmad B, Choi S. A structure-based drug discovery paradigm. Int J Mol Sci. 2019;20(11):2783. doi:10.3390/ijms20112783.
   PubMed Web of Science ®Google Scholar
• Schneider G. Future de novo drug design. Mol Inform. 2014;33(6–7):397–402. doi:10.1002/minf.201400034.
   PubMed Web of Science ®Google Scholar
• Liu X, Shi D, Zhou S, et al. Molecular dynamics simulations and novel drug discovery. Expert Opin Drug Discov. 2018;13(1):23–37. doi:10.1080/17460441.2018.1403419.
   PubMed Web of Science ®Google Scholar
• Durrant JD, Lindert S, McCammon JA. Autogrow 3.0: an improved algorithm for chemically tractable, semi-automated protein inhibitor design. J Mol Graphics Modell. 2013;44:104–112. doi:10.1016/j.jmgm.2013.05.006.
   Google Scholar
• Irwin JJ, Sterling T, Mysinger MM, et al. ZINC: a free tool to discover chemistry for biology. J Chem Inf Model. 2012;52(7):1757–1768. doi:10.1021/ci3001277.
   PubMed Web of Science ®Google Scholar
• Durrant JD, McCammon JA. Autoclickchem: click chemistry in silico. PLoS Comput Biol. 2012;8(3):e1002397. doi:10.1371/journal.pcbi.1002397.
   PubMed Web of Science ®Google Scholar
• Lindert S, Durrant JD, McCammon JA. Ligmerge: a fast algorithm to generate models of novel potential ligands from sets of known binders. Chem Biol Drug Des. 2012;80(3):358–365. doi:10.1111/j.1747-0285.2012.01414.x.
   PubMed Web of Science ®Google Scholar
• Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23(1–3):3–25. doi:10.1016/S0169-409X(96)00423-1.
   Web of Science ®Google Scholar
• Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem. 1999;1(1):55–68. doi:10.1021/cc9800071.
   PubMedGoogle Scholar
• Huang L, Brinen LS, Ellman JA. Crystal structures of reversible ketone-based inhibitors of the cysteine protease cruzain. Bioorg Med Chem. 2003;11(1):21–29. doi:10.1016/S0968-0896(02)00427-3.
   PubMed Web of Science ®Google Scholar
• Trott O, Olson AJ. Autodock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2009;31(2):NA–NA. doi:10.1002/jcc.21334.
   Web of Science ®Google Scholar
• Wu Z, Jiang D, Wang J, et al. Mining toxicity information from large amounts of toxicity data. J Med Chem. 2021;64(10):6924–6936. doi:10.1021/acs.jmedchem.1c00421.
   PubMed Web of Science ®Google Scholar
• Sander T, Freyss J, von Korff M, et al. OSIRIS, an entirely in-house developed drug discovery informatics system. J Chem Inf Model. 2009;49(2):232–246. doi:10.1021/ci800305f.
   PubMed Web of Science ®Google Scholar
• Jones G, Willett P, Glen RC, et al. Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. Cohen. J Mol Biol. 1997;267(3):727–748. doi:10.1006/jmbi.1996.0897.
   PubMed Web of Science ®Google Scholar
• Atanasova M, Stavrakov G, Philipova I, et al. Galantamine derivatives with indole moiety: docking, design, synthesis and acetylcholinesterase inhibitory activity. Bioorg Med Chem. 2015;23(17):5382–5389. doi:10.1016/j.bmc.2015.07.058.
   PubMed Web of Science ®Google Scholar
• Verdonk ML, Cole JC, Hartshorn MJ, et al. Improved protein-ligand docking using GOLD. Proteins Struct Funct Bioinf. 2003;52(4):609–623. doi:10.1002/prot.10465.
   PubMed Web of Science ®Google Scholar
• Stierand K, Rarey M. Poseview – molecular interaction patterns at a glance. J Cheminform. 2010;2(S1):P50. doi:10.1186/1758-2946-2-S1-P50.
   Google Scholar
• Salomon-Ferrer R, Götz AW, Poole D, et al. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle Mesh Ewald. J Chem Theory Comput. 2013;9(9):3878–3888. doi:10.1021/ct400314y.
   PubMed Web of Science ®Google Scholar
• Case DA, Walker RC, Cheatham TE, et al. Amber 18. San Francisco: University of California; 2018.
   Google Scholar
• Hariharan PC, Pople JA. The influence of polarization functions on molecular orbital hydrogenation energies. Theor Chim Acta. 1973;28(3):213–222. doi:10.1007/BF00533485.
   Google Scholar
• Frisch MJ, Trucks GW, Schlegel HB, et al. Gaussian09 Revision D.01, Gaussian Inc. Wallingford CT. In Gaussian 09 Revision C.01; 2010.
   Google Scholar
• Bayly CI, Cieplak P, Cornell W, et al. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J Phys Chem. 1993;97(40):10269–10280. doi:10.1021/j100142a004.
   Web of Science ®Google Scholar
• Wang J, Wolf RM, Caldwell JW, et al. Development and testing of a general amber force field. J Comput Chem. 2004;25(9):1157–1174. doi:10.1002/jcc.20035.
   PubMed Web of Science ®Google Scholar
• Maier JA, Martinez C, Kasavajhala K, et al. ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput. 2015;11(8):3696–3713. doi:10.1021/acs.jctc.5b00255.
   PubMed Web of Science ®Google Scholar
• Olsson MHM, Søndergaard CR, Rostkowski M, et al. PROPKA3: consistent treatment of internal and surface residues in empirical pKapredictions. J Chem Theory Comput. 2011;7(2):525–537. doi:10.1021/ct100578z.
   PubMed Web of Science ®Google Scholar
• Jorgensen WL, Chandrasekhar J, Madura JD, et al. Comparison of simple potential functions for simulating liquid water. J Chem Phys. 1983;79(2):926–935. doi:10.1063/1.445869.
   Web of Science ®Google Scholar
• Ryckaert J-P, Ciccotti G, Berendsen HJ. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys. 1977;23(3):327–341. doi:10.1016/0021-9991(77)90098-5.
   Web of Science ®Google Scholar
• 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(12):10089–10092. doi:10.1063/1.464397.
   Web of Science ®Google Scholar
• Roe DR, Cheatham TE. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013;9(7):3084–3095. doi:10.1021/ct400341p.
   PubMed Web of Science ®Google Scholar
• Srinivasan J, Cheatham TE, Cieplak P, et al. Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate−DNA helices. J Am Chem Soc. 1998;120(37):9401–9409. doi:10.1021/ja981844+.
   Web of Science ®Google Scholar
• Miller BR, McGee TD, Swails JM, et al. MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput. 2012;8(9):3314–3321. doi:10.1021/ct300418h.
   PubMed Web of Science ®Google Scholar
• Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin Drug Discov. 2015;10(5):449–461. doi:10.1517/17460441.2015.1032936.
   PubMed Web of Science ®Google Scholar
• Wang E, Sun H, Wang J, et al. End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chem Rev. 2019;119(16):9478–9508. doi:10.1021/acs.chemrev.9b00055.
   PubMed Web of Science ®Google Scholar
• Gupta A, Chaudhary N, Aparoy P. MM-PBSA and per-residue decomposition energy studies on 7-Phenyl-imidazoquinolin-4(5H)-one derivatives: identification of crucial site points at microsomal prostaglandin E synthase-1 (mPGES-1) active site. Int J Biol Macromol. 2018;119:352–359. doi:10.1016/j.ijbiomac.2018.07.050.
   PubMed Web of Science ®Google Scholar
• Zoete V, Michielin O. Comparison between computational alanine scanning and per-residue binding free energy decomposition for protein-protein association using MM-GBSA: application to the TCR-p-MHC complex. Proteins Struct Funct Bioinf. 2007;67(4):1026–1047. doi:10.1002/prot.21395.
   PubMed Web of Science ®Google Scholar
• Lockhat HA, Silva JRA, Alves CN, et al. Binding free energy calculations of nine FDA-approved protease inhibitors against HIV-1 subtype C I36T↑T containing 100 amino acids per monomer. Chem Biol Drug Des. 2016;87(4):487–498. doi:10.1111/cbdd.12690.
   PubMed Web of Science ®Google Scholar
• Martins LS, Lameira J, Kruger HG, et al. Evaluating the performance of a non-bonded Cu2+ model including Jahn−Teller effect into the binding of tyrosinase inhibitors. Int J Mol Sci. 2020;21(13):4783. doi:10.3390/ijms21134783.
   PubMed Web of Science ®Google Scholar
• Khan T, Ahmad R, Azad I, et al. Computer-aided drug design and virtual screening of targeted combinatorial libraries of mixed-ligand transition metal complexes of 2-butanone thiosemicarbazone. Comput Biol Chem. 2018;75:178–195. doi:10.1016/j.compbiolchem.2018.05.008.
   PubMed Web of Science ®Google Scholar
• Deconinck E, Ates H, Callebaut N, et al. Evaluation of chromatographic descriptors for the prediction of gastro-intestinal absorption of drugs. J Chromatogr A. 2007;1138(1–2):190–202. doi:10.1016/j.chroma.2006.10.068.
   PubMed Web of Science ®Google Scholar
• Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717–42729. doi:10.1038/srep42717.
   PubMed Web of Science ®Google Scholar
• Silva-Júnior EF, Silva EPS, França PHB, et al. Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi. Bioorg Med Chem. 2016;24(18):4228–4240. doi:10.1016/j.bmc.2016.07.013.
   PubMed Web of Science ®Google Scholar
• Brinen LS, Hansell E, Cheng J, et al. A target within the target: probing cruzain’s P1′ site to define structural determinants for the Chagas’ disease protease. Structure. 2000;8(8):831–840. doi:10.1016/S0969-2126(00)00173-8.
   PubMed Web of Science ®Google Scholar
• Turk D, Gunčar G, Podobnik M, et al. Revised definition of substrate binding sites of papain-like cysteine proteases. Biol Chem. 1998;379(2):137–148. doi:10.1515/bchm.1998.379.2.137.
   PubMed Web of Science ®Google Scholar
• Sajid M, Robertson SA, Brinen LS, et al. Cruzain. In: Advances in experimental medicine and biology. vol. 712; 2011. p. 100–115. doi:10.1007/978-1-4419-8414-2_7
   Google Scholar
• da Silva-Junior EF, Barcellos Franca PH, Ribeiro FF, et al. Molecular docking studies applied to a dataset of cruzain inhibitors. Curr Comput Aided Drug Des. 2018;14(1):68–78. doi:10.2174/1573409913666170519112758.
   PubMed Web of Science ®Google Scholar
• Herrera-Mayorga V, Lara-Ramírez E, Chacón-Vargas K, et al. Structure-based virtual screening and in vitro evaluation of new trypanosoma cruzi cruzain inhibitors. Int J Mol Sci. 2019;20(7):1742. doi:10.3390/ijms20071742.
   PubMed Web of Science ®Google Scholar
• Santos LH, Waldner BJ, Fuchs JE, et al. Understanding structure–activity relationships for trypanosomal cysteine protease inhibitors by simulations and free energy calculations. J Chem Inf Model. 2019;59(1):137–148. doi:10.1021/acs.jcim.8b00557.
   PubMed Web of Science ®Google Scholar
• dos Santos Filho JM, Leite ACL, Oliveira BGd, et al. Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorg Med Chem. 2009;17(18):6682–6691. doi:10.1016/j.bmc.2009.07.068.
   PubMed Web of Science ®Google Scholar
• Medeiros AR, Ferreira LLG, de Souza ML, et al. Chemoinformatics studies on a series of imidazoles as cruzain inhibitors. Biomolecules. 2021;11(4):579. doi:10.3390/biom11040579.
   PubMed Web of Science ®Google Scholar
• Durrant JD, Keränen H, Wilson BA, et al. Computational identification of uncharacterized cruzain binding sites. PLoS Negl Trop Dis. 2010;4(5):e676. doi:10.1371/journal.pntd.0000676.
   PubMed Web of Science ®Google Scholar
• dos Santos Nascimento IJ, de Aquino TM, da Silva-Júnior EF. Cruzain and rhodesain inhibitors: last decade of advances in seeking for new compounds against American and African Trypanosomiases. Curr Top Med Chem. 2021;21(21):1871–1899. doi:10.2174/1568026621666210331152702.
   PubMed Web of Science ®Google Scholar
• Rampogu S, Lee G, Baek A, et al. Discovery of non-peptidic compounds against chagas disease applying pharmacophore guided molecular modelling approaches. Molecules. 2018;23(12):3054. doi:10.3390/molecules23123054.
   PubMed Web of Science ®Google Scholar
• Santos VC, Oliveira AER, Campos ACB, et al. The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites. Sci Rep. 2021;11(1):18231. doi:10.1038/s41598-021-97490-2.
   PubMed Web of Science ®Google Scholar
• Hansen N, Van Gunsteren WF. Practical aspects of free-energy calculations: a review. J Chem Theory Comput. 2014;10(7):2632–2647. doi:10.1021/ct500161f.
   PubMed Web of Science ®Google Scholar
• Kitchen DB, Decornez H, Furr JR, et al. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discovery. 2004;3(11):935–949. doi:10.1038/nrd1549.
   PubMed Web of Science ®Google Scholar
• Hou T, Wang J, Li Y, et al. Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. J Chem Inf Model. 2011;51(1). doi:10.1021/ci100275a.
   PubMed Web of Science ®Google Scholar
• Hoelz LVB, Leal VF, Rodrigues CR, et al. Molecular dynamics simulations of the free and inhibitor-bound cruzain systems in aqueous solvent: insights on the inhibition mechanism in acidic pH. J Biomol Struct Dyn. 2016;34(9):1969–1978. doi:10.1080/07391102.2015.1100139.
   PubMed Web of Science ®Google Scholar