Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH20320 > Fulltext
RESEARCH ARTICLE
Contents Vol 74(7)

Conformers, Properties of the Anticancer Drug Plocabulin, and its Binding Mechanism with p-Glycoprotein: DFT and MD Studies

Xudong Lü A , Yufei Ma A , Yulian Tao A , Fei Yan A , Ce Song B C , Cuihong Wang https://orcid.org/0000-0002-9443-5237 D and Meiling Zhang https://orcid.org/0000-0002-8241-747X A E
+ Author Affiliations
- Author Affiliations

A School of Biomedical Engineering and Technology, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.

B Hefei National Laboratory of Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China.

C Department of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology, SE-10691 Stockholm, Sweden.

D School of Science, Tianjin Chengjian University, 26 Jinjing Road, Tianjin 300384, China.

E Corresponding author. Email: mlzhang@tmu.edu.cn

Australian Journal of Chemistry 74(7) 529-539 https://doi.org/10.1071/CH20320
Submitted: 23 October 2020  Accepted: 29 January 2021   Published: 8 March 2021

Abstract

Plocabulin (PM060184) is a promising new anticancer drug as a microtubule inhibitor. The conformational structure and properties of plocabulin have been studied theoretically. The initial structure was screened by the B3LYP/3-21G* method, and then 32 unique conformations were further optimised with the B3LYP/6-311G* method. The single-point energies were determined at the M06-L/6-311G(2df,p) level. The UV excitation of the most stable plocabulin conformation in methanol was studied by the TD-CAM-B3LYP/6-311G(2df,p) method. High-quality human p-glycoprotein model was obtained through homology modelling. The binding interaction between p-glycoprotein and plocabulin was studied by docking and MD simulation. LEU65, TYR310, ILE340, THR945, PHE983, MET986, and GLN990 were found to be important amino acid residues in the interaction. From a certain perspective, the ‘reverse exclusion’ mechanism of plocabulin with p-glycoprotein was illustrated, and this mechanism provides theoretical guidance for the structural modification of plocabulin and for design of drug’s to avoid p-glycoprotein-mediated drug resistance.


References

[1]  C. Dumontet, M. A. Jordan, Nat. Rev. Drug Discov. 2010, 9, 790.
         | Crossref | GoogleScholarGoogle Scholar | 20885410PubMed |

[2]  M. A. Jordan, L. Wilson, Nat. Rev. Cancer 2004, 4, 253.
         | Crossref | GoogleScholarGoogle Scholar | 15057285PubMed |

[3]  C. Calcabrini, E. Catanzaro, A. Bishayee, E. Turrini, C. Fimognari, Mar. Drugs 2017, 15, 310.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  M. J. Martín, L. Coello, R. Fernández, F. Reyes, A. Rodríguez, C. Murcia, et al. J. Am. Chem. Soc. 2013, 135, 10164.
         | Crossref | GoogleScholarGoogle Scholar | 23750450PubMed |

[5]  B. Pera, I. Barasoain, A. Pantazopoulou, A. Canales, R. Matesanz, J. Rodriguez-Salarichs, et al. ACS Chem. Biol. 2013, 8, 2084.
         | Crossref | GoogleScholarGoogle Scholar | 23859655PubMed |

[6]  M. Martínez-Díez, M. J. Guillén-Navarro, B. Pera, B. P. Bouchet, J. F. Martínez-Leal, I. Barasoain, et al. Biochem. Pharmacol. 2014, 88, 291.
         | Crossref | GoogleScholarGoogle Scholar | 24486569PubMed |

[7]  E. Elez, C. Gomez-Roca, A. Soto Matos-Pita, G. Argiles, T. Valentin, C. Coronado, et al. Invest. New Drugs 2019, 37, 674.
         | Crossref | GoogleScholarGoogle Scholar | 30411218PubMed |

[8]  A. E. Prota, K. Bargsten, J. F. Diaz, M. Marsh, C. Cuevas, M. Liniger, et al. Proc. Natl. Acad. Sci. USA 2014, 111, 13817.
         | Crossref | GoogleScholarGoogle Scholar | 25114240PubMed |

[9]  Y. Wang, A. Wozniak, J. Wellens, Y. K. Gebreyohannes, M. J. Guillén, P. M. Avilés, et al. Transl. Oncol. 2020, 13, 100832.
         | Crossref | GoogleScholarGoogle Scholar | 32898766PubMed |

[10]  K. R. Navarrete, V. A. Jiménez, J. Chem. Inf. Model. 2020, 60, 4076.
         | Crossref | GoogleScholarGoogle Scholar | 32687349PubMed |

[11]  W. T. Bellamy, Annu. Rev. Pharmacol. Toxicol. 1996, 36, 161.
         | Crossref | GoogleScholarGoogle Scholar | 8725386PubMed |

[12]  Q. Cui, J. Q. Wang, Y. G. Assaraf, L. Ren, P. Gupta, L. Wei, et al. Drug Resist. Updates 2018, 41, 1.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  N. K. Lytle, A. G. Barber, T. Reya, Nat. Rev. Cancer 2018, 18, 669.
         | Crossref | GoogleScholarGoogle Scholar | 30228301PubMed |

[14]  J. S. Lagas, R. A. van Waterschoot, R. W. Sparidans, E. Wagenaar, J. H. Beijnen, A. H. Schinkel, Mol. Cancer Ther. 2010, 9, 319.
         | Crossref | GoogleScholarGoogle Scholar | 20103600PubMed |

[15]  P. D. Eckford, F. J. Sharom, Chem. Rev. 2009, 109, 2989.
         | Crossref | GoogleScholarGoogle Scholar | 19583429PubMed |

[16]  J. Li, K. F. Jaimes, S. G. Aller, Protein Sci. 2014, 23, 34.
         | Crossref | GoogleScholarGoogle Scholar | 24155053PubMed |

[17]  A. B. Ward, P. Szewczyk, V. Grimard, C. W. Lee, L. Martinez, R. Doshi, et al. Proc. Natl. Acad. Sci. USA 2013, 110, 13386.
         | Crossref | GoogleScholarGoogle Scholar | 23901103PubMed |

[18]  M. S. Jin, M. L. Oldham, Q. Zhang, J. Chen, Nature 2012, 490, 566.
         | Crossref | GoogleScholarGoogle Scholar | 23000902PubMed |

[19]  S. G. Aller, J. Yu, A. Ward, Y. Weng, S. Chittaboina, R. Zhuo, et al. Science 2009, 323, 1718.
         | Crossref | GoogleScholarGoogle Scholar | 19325113PubMed |

[20]  E. P. Bruggemann, S. J. Currier, M. M. Gottesman, I. Pastan, J. Biol. Chem. 1992, 267, 21020.
         | Crossref | GoogleScholarGoogle Scholar | 1356986PubMed |

[21]  G. Scambia, F. O. Ranelletti, P. B. Panici, R. De Vincenzo, G. Bonanno, G. Ferrandina, et al. Cancer Chemother. Pharmacol. 1994, 34, 459.
         | Crossref | GoogleScholarGoogle Scholar | 7923555PubMed |

[22]  T. M. Sissung, C. E. Baum, J. Deeken, D. K. Price, J. Aragon-Ching, S. M. Steinberg, et al. Clin. Cancer Res. 2008, 14, 4543.
         | Crossref | GoogleScholarGoogle Scholar | 18628469PubMed |

[23]  R. W. Robey, K. M. Pluchino, M. D. Hall, A. T. Fojo, S. E. Bates, M. M. Gottesman, Nat. Rev. Cancer 2018, 18, 452.
         | Crossref | GoogleScholarGoogle Scholar | 29643473PubMed |

[24]  R. J. Kathawala, Y. J. Wang, S. Shukla, Y. K. Zhang, S. Alqahtani, A. Kaddoumi, et al. Chin. J. Cancer 2015, 34, 5.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  M. Zhang, C. Song, Z. Yao, Q. Ji, Curr. Org. Chem. 2012, 16, 2321.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  C. Sun, L. Zhu, C. Zhang, C. Song, C. Wang, M. Zhang, et al. J. Comput. Chem. 2018, 39, 889.
         | Crossref | GoogleScholarGoogle Scholar | 29330902PubMed |

[27]  L. Zhu, C. Zhang, X. Lü, C. Song, C. Wang, M. Zhang, et al. J. Mol. Model. 2020, 26, 162.
         | Crossref | GoogleScholarGoogle Scholar | 32474655PubMed |

[28]  S. Stepanian, I. Reva, E. Radchenko, L. Adamowicz, J. Phys. Chem. A 1998, 102, 4623.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  B. Schindler, G. Laloy-Borgna, L. Barnes, A. R. Allouche, E. Bouju, V. Dugas, et al. Anal. Chem. 2018, 90, 11741.
         | Crossref | GoogleScholarGoogle Scholar | 30152689PubMed |

[30]  P. A. Nikitina, T. Y. Koldaeva, V. S. Mityanov, V. S. Miroshnikov, E. I. Basanova, V. P. Perevalov, Aust. J. Chem. 2019, 72, 699.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  R. Zamiri, H. A. Ahangar, A. Kaushal, A. Zakaria, G. Zamiri, D. Tobaldi, et al. PLoS One 2015, 10, e0122989.
         | Crossref | GoogleScholarGoogle Scholar | 26135304PubMed |

[32]  A. Alam, J. Kowal, E. Broude, I. Roninson, K. P. Locher, Science 2019, 363, 753.
         | Crossref | GoogleScholarGoogle Scholar | 30765569PubMed |

[33]  R. Kumari, R. Kumar, C. Open Source Drug Discovery, A. Lynn, J. Chem. Inf. Model. 2014, 54, 1951.
         | Crossref | GoogleScholarGoogle Scholar | 24850022PubMed |

[34]  M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09 2009 (Gaussian, Inc.: Wallingford, CT).

[35]  V. S. Bernales, A. V. Marenich, R. Contreras, C. J. Cramer, D. G. Truhlar, J. Phys. Chem. B 2012, 116, 9122.
         | Crossref | GoogleScholarGoogle Scholar | 22734466PubMed |

[36]  E. Seifert, J. Chem. Inf. Model. 2014, 54, 1552.
         | Crossref | GoogleScholarGoogle Scholar | 24702057PubMed |

[37]  Y. Kim, J. Chen, Science 2018, 359, 915.
         | Crossref | GoogleScholarGoogle Scholar | 29371429PubMed |

[38]  A. Alam, R. Küng, J. Kowal, R. A. McLeod, N. Tremp, E. V. Broude, et al. Proc. Natl. Acad. Sci. USA 2018, 115, E1973.
         | Crossref | GoogleScholarGoogle Scholar | 29440498PubMed |

[39]  The UniProt Consortium Nucleic Acids Res. 2018, 46, 2699.
         | Crossref | GoogleScholarGoogle Scholar | 29425356PubMed |

[40]  H. McWilliam, W. Li, M. Uludag, S. Squizzato, Y. M. Park, N. Buso, et al. Nucleic Acids Res. 2013, 41, W597.
         | Crossref | GoogleScholarGoogle Scholar | 23671338PubMed |

[41]  A. Waterhouse, M. Bertoni, S. Bienert, G. Studer, G. Tauriello, R. Gumienny, et al. Nucleic Acids Res. 2018, 46, W296.
         | Crossref | GoogleScholarGoogle Scholar | 29788355PubMed |

[42]  T. Schwede, J. Kopp, N. Guex, M. C. Peitsch, Nucleic Acids Res. 2003, 31, 3381.
         | Crossref | GoogleScholarGoogle Scholar | 12824332PubMed |

[43]  N. Guex, M. C. Peitsch, T. Schwede, Electrophoresis 2009, 30, S162.
         | Crossref | GoogleScholarGoogle Scholar | 19517507PubMed |

[44]  A. E. Lohning, S. M. Levonis, B. Williams-Noonan, S. S. Schweiker, Curr. Top. Med. Chem. 2017, 17, 2023.
         | Crossref | GoogleScholarGoogle Scholar | 28137238PubMed |

[45]  Z. Li, F. Zhang, C. Zhang, C. Wang, P. Lu, X. Zhao, et al. Mol. Immunol. 2019, 114, 651.
         | Crossref | GoogleScholarGoogle Scholar | 31557626PubMed |

[46]  P. Rotkiewicz, J. Skolnick, J. Comput. Chem. 2008, 29, 1460.
         | Crossref | GoogleScholarGoogle Scholar | 18196502PubMed |

[47]  R. A. Laskowski, M. W. MacArthur, D. S. Moss, J. M. Thornton, J. Appl. Cryst. 1993, 26, 283.
         | Crossref | GoogleScholarGoogle Scholar |

[48]  C. Colovos, T. O. Yeates, Protein Sci. 1993, 2, 1511.
         | Crossref | GoogleScholarGoogle Scholar | 8401235PubMed |

[49]  P. Benkert, M. Künzli, T. Schwede, Nucleic Acids Res. 2009, 37, W510.
         | Crossref | GoogleScholarGoogle Scholar | 19429685PubMed |

[50]  S. Forli, R. Huey, M. E. Pique, M. F. Sanner, D. S. Goodsell, A. J. Olson, Nat. Protoc. 2016, 11, 905.
         | Crossref | GoogleScholarGoogle Scholar | 27077332PubMed |

[51]  M. Kontoyianni, Methods Mol. Biol. 2017, 1647, 255.
         | Crossref | GoogleScholarGoogle Scholar | 28809009PubMed |

[52]  Y. S. Mary, Y. S. Mary, K. S. Resmi, R. Thomas, Heliyon 2019, 5, e02175.
         | Crossref | GoogleScholarGoogle Scholar | 31763480PubMed |

[53]  B. V. Farahani, G. R. Bardajee, F. H. Rajabi, Z. Hooshyar, Aust. J. Chem. 2015, 68, 999.
         | Crossref | GoogleScholarGoogle Scholar |

[54]  G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, et al. J. Comput. Chem. 2009, 30, 2785.
         | Crossref | GoogleScholarGoogle Scholar | 19399780PubMed |

[55]  S. A. Showalter, R. Brüschweiler, J. Chem. Theory Comput. 2007, 3, 961.
         | Crossref | GoogleScholarGoogle Scholar | 26627416PubMed |

[56]  D. Van Der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, H. J. Berendsen, J. Comput. Chem. 2005, 26, 1701.
         | Crossref | GoogleScholarGoogle Scholar | 16211538PubMed |

[57]  K. G. Sprenger, V. W. Jaeger, J. Pfaendtner, J. Phys. Chem. B 2015, 119, 5882.
         | Crossref | GoogleScholarGoogle Scholar | 25853313PubMed |

[58]  G. Bussi, D. Donadio, M. Parrinello, J. Chem. Phys. 2007, 126, 014101.
         | Crossref | GoogleScholarGoogle Scholar | 17212484PubMed |

[59]  M. Parrinello, A. Rahman, J. Appl. Phys. 1981, 52, 7182.
         | Crossref | GoogleScholarGoogle Scholar |

[60]  B. Hess, H. Bekker, H. J. C. Berendsen, J. G. E. M. Fraaije, J. Comput. Chem. 1997, 18, 1463.
         | Crossref | GoogleScholarGoogle Scholar |

[61]  U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee, L. G. Pedersen, J. Chem. Phys. 1995, 103, 8577.
         | Crossref | GoogleScholarGoogle Scholar |

[62]  R. E. Rigsby, A. B. Parker, Biochem. Mol. Biol. Educ. 2016, 44, 433.
         | Crossref | GoogleScholarGoogle Scholar | 27241834PubMed |

[63]  E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, et al. J. Comput. Chem. 2004, 25, 1605.
         | Crossref | GoogleScholarGoogle Scholar | 15264254PubMed |