Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi


Цитировать

Полный текст

Аннотация

Background:Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment.

Objective:Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand.

Results:Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target.

Conclusion:Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

Об авторах

Yasmim Rocha

Graduate Program in Pharmaceutical Sciences, Federal University of Ceará

Email: info@benthamscience.net

Gabriel de Moura

Graduate Program in Pharmaceutical Sciences, Federal University of Ceará

Email: info@benthamscience.net

João Rodrigues

Graduate Program in Pharmaceutical Sciences, Federal University of Ceará

Email: info@benthamscience.net

Cristian Pinheiro

Graduate Program in Pharmaceutical Sciences, Federal University of Ceará

Email: info@benthamscience.net

Ronaldo de Oliveira

Department of Organic Chemistry, Rural Federal University of Pernambuco

Email: info@benthamscience.net

Marcia Marinho

Department of Chemistry, Ceara State University

Email: info@benthamscience.net

Roberto Nicolete

Graduate Program in Pharmaceutical Sciences, Federal University of Ceará

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Stanaway, J.D.; Roth, G. The burden of Chagas disease: Estimates and challenges. Glob. Heart, 2015, 10(3), 139-144. doi: 10.1016/j.gheart.2015.06.001 PMID: 26407508
  2. Trachtenberg, B.H.; Hare, J.M. Inflammatory cardiomyopathic syndromes. Circ. Res., 2017, 121(7), 803-818. doi: 10.1161/CIRCRESAHA.117.310221 PMID: 28912184
  3. Cantey, P.T.; Stramer, S.L.; Townsend, R.L.; Kamel, H.; Ofafa, K.; Todd, C.W.; Currier, M.; Hand, S.; Varnado, W.; Dotson, E.; Hall, C.; Jett, P.L.; Montgomery, S.P. The United States trypanosoma cruzi infection study: Evidence for vector-borne transmission of the parasite that causes Chagas disease among United States blood donors. Transfusion, 2012, 52(9), 1922-1930. doi: 10.1111/j.1537-2995.2012.03581.x PMID: 22404755
  4. Antunes, D.; Marins-Dos-Santos, A.; Ramos, M.T.; Mascarenhas, B.A.S.; Moreira, C.J.C.; Farias-de-Oliveira, D.A.; Savino, W.; Monteiro, R.Q.; de Meis, J. Oral route driven acute Trypanosoma cruzi infection unravels an IL-6 dependent hemostatic derangement. Front. Immunol., 2019, 10, 1073. doi: 10.3389/fimmu.2019.01073 PMID: 31139194
  5. Santos, M. Oral trypanosoma cruzi acute infection in mice targets primary lymphoid organs and triggers extramedullary hematopoiesis. Front. Cell. Infect. Microbiol., 2022, 12, 800395.
  6. Ferreira, R.R.; de Souza, E.M.; Vilar-Pereira, G.; Degrave, W.M.S.; Abreu, R.S.; Meuser-Batista, M.; Ferreira, N.V.C.; Ledbeter, S.; Barker, R.H.; Bailly, S.; Feige, J.J.; Lannes-Vieira, J.; de Araújo-Jorge, T.C.; Waghabi, M.C. In Chagas disease, transforming growth factor beta neutralization reduces Trypanosoma cruzi infection and improves cardiac performance. Front. Cell. Infect. Microbiol., 2022, 12, 1017040. doi: 10.3389/fcimb.2022.1017040 PMID: 36530434
  7. Crespillo-Andújar, C.; Venanzi-Rullo, E.; López-Vélez, R.; Monge-Maillo, B.; Norman, F.; López-Polín, A.; Pérez-Molina, J.A. Safety profile of benznidazole in the treatment of chronic Chagas disease: Experience of a referral center and systematic literature review with meta-analysis. Drug Saf., 2018, 41(11), 1035-1048. doi: 10.1007/s40264-018-0696-5 PMID: 30006773
  8. Yang, S.; Ren, C.L.; Ma, T.Y.; Zou, W.Q.; Dai, L.; Tian, X.Y.; Liu, X.H.; Tan, C.X. 1, 2, 4-Oxadiazole-based bio-isosteres of benzamides: Synthesis, biological activity, and toxicity to zebrafish embryo. Int. J. Mol. Sci., 2021, 22(5), 2367. doi: 10.3390/ijms22052367 PMID: 33673430
  9. Vaidya, A.; Jain, S.; Prashantha Kumar, B.; Singh, S.K.; Kashaw, S.K.; Agrawal, R.K. Synthesis of 1,2,4-oxadiazole derivatives: Anticancer and 3D QSAR studies. Monatsh. Chem., 2020, 151(3), 385-395. doi: 10.1007/s00706-020-02553-1
  10. Vaidya, A.; Jain, S.; Jain, P.; Jain, P.; Tiwari, N.; Jain, R.; Jain, R.; Jain, A.K.; Agrawal, R.K. Synthesis, and biological activities of oxadiazole derivatives: A review. Mini Rev. Med. Chem., 2016, 16(10), 825-845. doi: 10.2174/1389557516666160211120835 PMID: 26864552
  11. Rocha, Y.M.; Magalhães, E.P.; de Medeiros, C.M.; Machado, M.M. Nascimento e Melo de Oliveira, V.; de Oliveira, N.R.; Lima Sampaio, T.; de Menezes, R.R.P.P.B.; Martins, A.M.C.; Nicolete, R. Antiparasitary and antiproliferative activities in vitro of a 1,2,4-oxadiazole derivative on Trypanosoma cruzi. Parasitol. Res., 2022, 121(7), 2141-2156. doi: 10.1007/s00436-022-07554-z PMID: 35610523
  12. Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4(1), 17. doi: 10.1186/1758-2946-4-17 PMID: 22889332
  13. Brak, K.; Kerr, I.D.; Barrett, K.T.; Fuchi, N.; Debnath, M.; Ang, K.; Engel, J.C.; McKerrow, J.H.; Doyle, P.S.; Brinen, L.S.; Ellman, J.A.; Ellman, J. Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J. Med. Chem., 2010, 53(4), 1763-1773. doi: 10.1021/jm901633v PMID: 20088534
  14. Yan, J.; Zhang, G.; Pan, J.; Wang, Y. α-Glucosidase inhibition by luteolin: Kinetics, interaction and molecular docking. Int. J. Biol. Macromol., 2014, 64, 213-223. doi: 10.1016/j.ijbiomac.2013.12.007 PMID: 24333230
  15. Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791. doi: 10.1002/jcc.21256 PMID: 19399780
  16. 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., 2009, 31(2), NA. doi: 10.1002/jcc.21334 PMID: 19499576
  17. Shityakov, S.; Förster, C. In silico predictive model to determine vector-mediated transport properties for the blood-brain barrier choline transporter. Adv. Appl. Bioinforma. Chem., 2014, 7, 23-36. doi: 10.2147/AABC.S63749
  18. Yusuf, D.; Davis, A.M.; Kleywegt, G.J.; Schmitt, S. An alternative method for the evaluation of docking performance: RSR vs RMSD. J. Chem. Inf. Model., 2008, 48(7), 1411-1422. doi: 10.1021/ci800084x PMID: 18598022
  19. Imberty, A.; Hardman, K.D.; Carver, J.P.; Pérez, S. Molecular modelling of protein-carbohydrate interactions. Docking of monosaccharides in the binding site of concanavalin A. Glycobiology, 1991, 1(6), 631-642. doi: 10.1093/glycob/1.6.631 PMID: 1822243
  20. Berendsen, H.J.C.; van der Spoel, D.; van Drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation. Comput. Phys. Commun., 1995, 91(1-3), 43-56. doi: 10.1016/0010-4655(95)00042-E
  21. MacKerell, A.D., Jr; Banavali, N.; Foloppe, N. Development and current status of the CHARMM force field for nucleic acids. Biopolymers, 2000, 56(4), 257-265. doi: 10.1002/1097-0282(2000)56:43.0.CO;2-W PMID: 11754339
  22. Zoete, V.; Cuendet, M.A.; Grosdidier, A.; Michielin, O. SwissParam: A fast force field generation tool for small organic molecules. J. Comput. Chem., 2011, 32(11), 2359-2368. doi: 10.1002/jcc.21816 PMID: 21541964
  23. Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys., 2007, 126(1), 014101. doi: 10.1063/1.2408420 PMID: 17212484
  24. Parrinello, M.; Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys., 1981, 52(12), 7182-7190. doi: 10.1063/1.328693
  25. Van Gunsteren, W.F.; Berendsen, H.J.C. A leap-frog algorithm for stochastic dynamics. Mol. Simul., 1988, 1(3), 173-185. doi: 10.1080/08927028808080941
  26. Vargas, E.; Echeverri, F.; Vélez, I.; Robledo, S.; Quiñones, W. Synthesis and evaluation of thiochroman-4-one derivatives as potential leishmanicidal agents. Molecules, 2017, 22(12), 2041. doi: 10.3390/molecules22122041 PMID: 29186046
  27. Scharfstein, J. Subverting bradykinin-evoked inflammation by co-opting the contact system. Curr. Opin. Hematol., 2018, 25(5), 347-357. doi: 10.1097/MOH.0000000000000444 PMID: 30028741
  28. Tomas, A.M. Overexpression of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, is associated with enhanced metacyclogenesis. Eur. J. Biochem., 1997, 244(2), 596-603.
  29. Caputto, M.E.; Fabian, L.E.; Benítez, D.; Merlino, A.; Ríos, N.; Cerecetto, H.; Moltrasio, G.Y.; Moglioni, A.G.; González, M.; Finkielsztein, L.M. Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents. Bioorg. Med. Chem., 2011, 19(22), 6818-6826. doi: 10.1016/j.bmc.2011.09.037 PMID: 22000947
  30. Deb, P.K.; Al-Shar’i, N.A.; Venugopala, K.N.; Pillay, M.; Borah, P. In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 869-884. doi: 10.1080/14756366.2021.1900162 PMID: 34060396

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Bentham Science Publishers, 2024