683
Views
5
CrossRef citations to date
0
Altmetric
Research Article

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

, ORCID Icon, , ORCID Icon & ORCID Icon
Pages 325-345 | Received 17 Dec 2019, Accepted 20 Feb 2020, Published online: 16 Mar 2020

References

  • S.A. Amin, N. Adhikari, and T. Jha, Design of aminopeptidase N inhibitors as anti-cancer agents, J. Med. Chem. 61 (2018), pp. 6468–6490. doi:10.1021/acs.jmedchem.7b00782.
  • P. Mina-Osorio, The moonlighting enzyme CD13: Old and new functions to target, Trends Mol. Med. 14 (2008), pp. 361–371. doi:10.1016/j.molmed.2008.06.003.
  • D. Reinhold, A. Biton, S. Pieper, U. Lendeckel, J. Faust, K. Neubert, U. Bank, M. Täger, S. Ansorge, and S. Brocke, Dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) as regulators of T cell function and targets of immunotherapy in CNS inflammation, Int. Immunopharmacol. 6 (2006), pp. 1935–1942. doi:10.1016/j.intimp.2006.07.023.
  • L. Chen, Y.L. Lin, G. Peng, and F. Li, Structural basis for multifunctional roles of mammalian aminopeptidase N, Proc. Natl. Acad. Sci. USA 109 (2012), pp. 17966–17971. doi:10.1073/pnas.1210123109.
  • N.M. Hooper, Families of zinc metalloproteases, FEBS Lett. 354 (1994), pp. 1–6. doi:10.1016/0014-5793(94)01079-X.
  • A.N. Santos, J. Langner, M. Herrmann, and D. Riemann, Aminopeptidase N/CD13 is directly linked to signal transduction pathways in monocytes, Cell. Immunol. 201 (2000), pp. 22−32. doi:10.1006/cimm.2000.1629.
  • S.L. Larsen, L.O. Pedersen, S. Buus, and A. Stryhn, T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides, J. Exp. Med. 184 (1996), pp. 183–189. doi:10.1084/jem.184.1.183.
  • I. Saiki, J. Yoneda, I. Azuma, H. Fujii, F. Abe, M. Nakajima, and T. Tsuruo, Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation, Int. J. Cancer 54 (1993), pp. 137–143. doi:10.1002/()1097-0215.
  • C. Liu, Y. Yang, L. Chen, Y.-L. Lin, and L. Fang, A unified mechanism for aminopeptidase N-based tumor cell motility and tumor-homing therapy, J. Biol. Chem. 289 (2014), pp. 34520–34529. doi:10.1074/jbc.M114.566802.
  • D.E. Wentworth and K.V. Holmes, Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): Influence of N-linked glycosylation, J. Virol. 75 (2001), pp. 9741–9752. doi:10.1128/JVI.75.20.9741-9752.2001.
  • A.F. Kolb, A. Hegyi, J. Maile, A. Heister, M. Hagemann, and S.G. Siddell, Molecular analysis of the coronavirus-receptor function of aminopeptidase N, Adv. Exp. Med. Biol. 440 (1998), pp. 61–67.
  • S.M. Tusell, S.A. Schittone, and K.V. Holmes, Mutational analysis of aminopeptidase N, a receptor for several group 1 coronaviruses, identifies key determinants of viral host range, J. Virol. 81 (2007), pp. 1261–1273. doi:10.1128/JVI.01510-06.
  • M. Wickström, R. Larsson, P. Nygren, and J. Gullbo, Aminopeptidase N (CD13) as a target for cancer chemotherapy, Cancer Sci. 102 (2011), pp. 501−508. doi:10.1111/j.1349-7006.2010.01826.x.
  • J.M. Martínez, I. Prieto, M.J. Ramírez, C. Cueva, F. Alba, and M. Ramírez, Aminopeptidase activities in breast cancer tissue, Clin. Chem. 45 (1999), pp. 1797–1802.
  • G. Severini, L. Gentilini, and C. Tirelli, Diagnostic evaluation of alanine aminopeptidase as serum marker for detecting cancer, Cancer Biochem. Biophys. 12 (1991), pp. 199–204.
  • P. Surowiak, M. Drąg, V. Materna, S. Suchocki, R. Grzywa, M. Spaczyński, M. Dietel, J. Oleksyszyn, M. Zabel, and H. Lage, Expression of aminopeptidase N/CD13 in human ovarian cancers, Int. J. Gynecol. Cancer 16 (2006), pp. 1783–1788. doi:10.1111/j.1525-1438.2006.00657.x.
  • M. Terauchi, H. Kajiyama, K. Shibata, K. Ino, A. Nawa, S. Mizutani, and F. Kikkawa, Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells, BMC Cancer 7 (2007), pp. 140. doi:10.1186/1471-2407-7-140.
  • H. Tsukamoto, K. Shibata, H. Kajiyama, M. Terauchi, A. Nawa, and F. Kikkawa, Aminopeptidase N (APN)/CD13 inhibitor, Ubenimex, enhances radiation sensitivity in human cervical cancer, BMC Cancer. 8 (2008), pp. 74. doi:10.1186/1471-2407-8-74.
  • X. Wang, Z. Niu, Y. Jia, M. Cui, L. Han, Y. Zhang, Z. Liu, D. Bi, and S. Liu, Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells, Oncol. Rep. 35 (2016), pp. 2121–2130. doi:10.3892/or.2016.4611.
  • N. Haraguchi, H. Ishii, K. Mimori, F. Tanaka, M. Ohkuma, H.M. Kim, H. Akita, D. Takiuchi, H. Hatano, H. Nagano, and G.F. Barnard, CD13 is a therapeutic target in human liver cancer stem cells, J. Clin. Invest. 120 (2010), pp. 3326–3339. doi:10.1172/JCI42550.
  • H. Hashida, A. Takabayashi, M. Kanai, M. Adachi, K. Kondo, N. Kohno, Y. Yamaoka, and M. Miyake, Aminopeptidase N is involved in cell motility and angiogenesis: Its clinical significance in human colon cancer, Gastroenterology 122 (2002), pp. 376–386. doi:10.1053/gast.2002.31095.
  • N. Ikeda, Y. Nakajima, T. Tokuhara, N. Hattori, M. Sho, H. Kanehiro, and M. Miyake, Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma, Clin. Cancer Res. 9 (2003), pp. 1503–1508.
  • A. Kido, S. Krueger, C. Haeckel, and A. Roessner, Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines, Clin. Exp. Metastasis 17 (1999), pp. 857–863. doi:10.1023/A:1006794617406.
  • L. Pang, N. Zhang, Y. Xia, D. Wang, G. Wang, and X. Meng, Serum APN/CD13 as a novel diagnostic and prognostic biomarker of pancreatic cancer, Oncotarget 7 (2016), pp. 77854–77864. doi:10.18632/oncotarget.v7i47.
  • Y. Inagaki, W. Tang, L. Zhang, G. Du, W. Xu, and N. Kokudo, Novel aminopeptidase N (APN/CD13) inhibitor 24F can suppress invasion of hepatocellular carcinoma cells as well as angiogenesis, Biosci. Trends 4 (2010), pp. 56–60.
  • L. Guzman-Rojas, R. Rangel, A. Salameh, J.K. Edwards, E. Dondossola, Y.G. Kim, A. Saghatelian, R.J. Giordano, M.G. Kolonin, F.I. Staquicini, and E. Koivunen, Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment, Proc. Natl. Acad. Sci. USA 109 (2012), pp. 1637–1642. doi:10.1073/pnas.1120790109.
  • H. Umezawa, T. Aoyagi, H. Suda, M. Hamada, and T. Takeuchi, Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes, J. Antibiot. 29 (1976), pp. 97–99. doi:10.7164/antibiotics.29.97.
  • D.H. Rich, B.J. Moon, and S. Harbeson, Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes, J. Med. Chem. 27 (1984), pp. 417–422. doi:10.1021/jm00370a001.
  • B.R. Lampret, J. Kidri, B. Kralj, L. Vitale, M. Pokorny, and M. Renko, Lapstatin, a new aminopeptidase inhibitor produced by Streptomyces rimosus, inhibits autogenous aminopeptidases, Arch. Microbiol. 171 (1999), pp. 397–404. doi:10.1007/s002030050726.
  • M. Nagai, F. Kojima, H. Naganawa, M. Hamada, T. Aoyagi, and T. Takeuchi, Phebestin, a new inhibitor of aminopeptidase N, produced by Streptomyces sp. MJ716-m3, J. Antibiot. 50 (1997), pp. 82–84. doi:10.7164/antibiotics.50.82.
  • L. Su, Y. Jia, L. Zhang, Y. Xu, H. Fang, and W. Xu, Design, synthesis and biological evaluation of novel amino acid ureido derivatives as aminopeptidase N/CD13 inhibitors, Bioorg. Med. Chem. 19 (2012), pp. 900–906. doi:10.1016/j.bmc.2010.11.066.
  • L. Su, Y. Jia, L. Zhang, Y. Xu, H. Fang, and W. Xu, Design, synthesis and biological evaluation of novel amino acid ureido derivatives as aminopeptidase N/CD13 inhibitors, Bioorg. Med. Chem. 20 (2012), pp. 3807–3815. doi:10.1016/j.bmc.2012.04.035.
  • L. Su, J. Cao, Y. Jia, X. Zhang, H. Fang, and W. Xu, Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis, ACS Med. Chem. Lett. 3 (2012), pp. 959–964. doi:10.1021/ml3000758.
  • C. Ma, K. Jin, J. Cao, L. Zhang, X. Li, and W. Xu, Novel leucine ureido derivatives as inhibitors of aminopeptidase N (APN), Bioorg. Med. Chem. 21 (2013), pp. 1621–1627. doi:10.1016/j.bmc.2013.01.068.
  • C. Ma, J. Cao, X. Liang, Y. Huang, P. Wu, Y. Li, W. Xu, and Y. Zhang, Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation, Eur. J. Med. Chem. 108 (2016), pp. 21–27. doi:10.1016/j.ejmech.2015.11.021.
  • J. Devillers, A. Larghi, and C. Lagneau, QSAR modelling of synergists to increase the efficacy of deltamethrin against pyrethroid-resistant Aedes aegypti mosquitoes, SAR QSAR Environ. Res. 29 (2018), pp. 613–629. doi:10.1080/1062936X.2018.1503846.
  • J.P. Doucet, E. Papa, A. Doucet-Panaye, and J. Devillers, QSAR models for predicting the toxicity of piperidine derivatives against Aedes aegypti, SAR QSAR Environ. Res. 28 (2017), pp. 451–470. doi:10.1080/1062936X.2017.1328855.
  • D. López-Malo, J.I. Bueso-Bordils, M.J. Duart, P.A. Alemán-López, R.V. Martín-Algarra, G.M. Antón-Fos, L. Lahuerta-Zamora, and J. Martínez-Calatayud, QSPR studies on the photoinduced-fluorescence behaviour of pharmaceuticals and pesticides, SAR QSAR Environ. Res. 28 (2017), pp. 609–620. doi:10.1080/1062936X.2017.1358212.
  • ChemDraw Ultra 5.0. Cambridge Soft Corporation, USA, 2010; software available at http://www.cambridgesoft.com.
  • DRAGON 6.0. TALETE SRL: Italy, 2001; Available at http://www.talete.mi.it/products/dragon_description.htm.
  • S. Banerjee, N. Adhikari, S.A. Amin, and T. Jha, Structural exploration of tetrahydroisoquinoline derivatives as HDAC8 inhibitors through multi-QSAR modeling study, J. Biomol. Struct. Dyn. (2019), pp. 1–14. (In press). doi:10.1080/07391102.2019.1617782.
  • S.A. Amin, N. Adhikari, S. Bhargava, T. Jha, and S. Gayen, Structural exploration of hydroxyethylamines as HIV-1 protease inhibitors: New features identified, SAR QSAR Environ. Res. 29 (2018), pp. 385–408. doi:10.1080/1062936X.2018.1447511.
  • S. Sanyal, S.A. Amin, N. Adhikari, and T. Jha, QSAR modelling on a series of arylsulfonamide-based hydroxamates as potent MMP-2 inhibitors, SAR QSAR Environ. Res. 30 (2019), pp. 247–263. doi:10.1080/1062936X.2019.1588159.
  • M. Hall, E. Frank, G. Holmes, B. Pfahringer, P. Reutemann, and I.H. Witten, The WEKA data mining software: An update, SIGKDD Explor. 11 (2009), pp. 10–18. doi:10.1145/1656274.1656278.
  • S.K. Baidya, S.A. Amin, S. Banerjee, N. Adhikari, and T. Jha, Structural exploration of arylsulfonamide-based ADAM17 inhibitors through validated comparative multi-QSAR modelling studies, J. Mol. Struct. 1185 (2019), pp. 128–142. doi:10.1016/j.molstruc.2019.02.081.
  • QSAR tools. DTC laboratory, India, 2020; software available at https://dtclab.webs.com/software-tools.
  • S.A. Amin, N. Adhikari, S. Bhargava, S. Gayen, and T. Jha, An integrated QSAR modeling approach to explore the structure–property and selectivity relationships of N-benzoyl-L-biphenylalanines as integrin antagonists, Mol. Divers. 22 (2018), pp. 129–158. doi:10.1007/s11030-017-9789-9.
  • K. Roy, S. Kar, and R.N. Das, Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment, Academic Press, London, 2015.
  • S.A. Amin, N. Adhikari, S. Gayen, and T. Jha, First report on the structural exploration and prediction of new BPTES analogs as glutaminase inhibitors, J. Mol. Struct. 1143 (2017), pp. 49–64. doi:10.1016/j.molstruc.2017.04.020.
  • STATISTICA Version 7. Statistical Software of StatSoft, Inc., Tulsa, USA; software available at http://www.statsoft.com.
  • N. Adhikari, S.A. Amin, A. Saha, and T. Jha, Exploring in house glutamate inhibitors of matrix metalloproteinase-2 through validated robust chemico-biological quantitative approaches, Struct. Chem. 29 (2018), pp. 285–297. doi:10.1007/s11224-017-1028-6.
  • E. Goya-Jorge, T.Q. Doan, M.L. Scippo, M. Muller, R.M. Giner, S.J. Barigye, and R. Gozalbes, Elucidating the aryl hydrocarbon receptor antagonism from a chemical-structural perspective, SAR QSAR Environ. Res. 31 (2020), pp. 209–226. doi:10.1080/1062936X.2019.1708460.
  • J.A. Castillo-Garit, G.M. Casañola-Martin, S.J. Barigye, H. Pham-The, F. Torrens, and A. Torreblanca, Machine learning-based models to predict modes of toxic action of phenols to Tetrahymena pyriformis, SAR QSAR Environ. Res. 28 (2017), pp. 735–747. doi:10.1080/1062936X.2017.1376705.
  • J.O. Berger, Statistical Decision Theory and Bayesian Analysis, Springer Science & Business Media, USA, 2013.
  • G.E.P. Box and G.C. Tiao, Bayesian Inference in Statistical Analysis, John Wiley & Sons, USA, 2011.
  • T. Jha, N. Adhikari, A. Saha, and S.A. Amin, Multiple molecular modelling studies on some derivatives and analogues of glutamic acid as matrix metalloproteinase-2 inhibitors, SAR QSAR Environ. Res. 29 (2018), pp. 43–68. doi:10.1080/1062936X.2017.1406986.
  • B. Bhardwaj, A.T.K. Baidya, S.A. Amin, N. Adhikari, T. Jha, and S. Gayen, Insight into structural features of phenyltetrazole derivatives as ABCG2 inhibitors for the treatment of multidrug resistance in cancer, SAR QSAR Environ. Res. 30 (2019), pp. 457–475. doi:10.1080/1062936X.2019.1615545.
  • Discovery Studio 3.0 (DS 3.0). Accelrys Inc., CA, USA, 2015; software available at http://www.accelrys.com.
  • A. Golbraikh and A. Tropsha, Beware of q2!, J. Mol. Graph. Model 20 (2002), pp. 269–276. doi:10.1016/S1093-3263(01)00123-1.
  • Q. Wang, M. Chen, H. Zhu, J. Zhang, H. Fang, B. Wang, and W. Xu, Design, synthesis, and QSAR studies of novel lysine derives as amino-peptidase N/CD13 inhibitors, Bioorg. Med. Chem. 16 (2008), pp. 5473–5481. doi:10.1016/j.bmc.2008.04.012.
  • X. Wang, F. Jing, H. Zhu, H. Fang, J. Zhang, and W. Xu, Activity screening and structure-activity relationship of the hit compounds targeting APN/CD13, Fundam. Clin. Pharmacol. 25 (2011), pp. 217–228. doi:10.1111/j.1472-8206.2010.00844.x.
  • Y. Xu, L. Zhang, M. Li, W. Xu, H. Fang, and L. Shang, QSAR studies of aminopeptidase N/CD13 (APN) inhibitors with the scaffold 3-phenylpropane-1,2-diamine and molecular docking, Med. Chem. Res. 21 (2012), pp. 1000–1015. doi:10.1007/s00044-011-9597-1.
  • A.K. Halder, A. Saha, and T. Jha, Exploration of structural and physicochemical requirements and search of virtual hits for aminopeptidase N inhibitors, Mol. Divers. 17 (2013), pp. 123–137. doi:10.1007/s11030-013-9422-5.
  • X. Tang, Q. Qu, B. Kuang, S. Li, and G. Tu, 3D-QSAR studies on flavone-8-acetic acid derivatives of aminopeptidase N inhibitors, Med. Chem. 11 (2015), pp. 764–770. doi:10.2174/1573406411666150714111256.
  • Q. Qu, X. Tang, B. Kuang, S. Li, and G. Tu, 3D-QSAR studies, molecular dynamics simulation and free energy calculation of APN inhibitors, Int. J. Pharmacol. 11 (2015), pp. 920–928. doi:10.3923/ijp.2015.920.928.
  • O. Farsa and M. Haluska, A single-and multiparametric QSAR study of aminopeptidase N inhibitors, FARMACIA 64 (2016), pp. 283–290.
  • J. Ziemska, J. Solecka, and M. Jaron´czyk, QSAR, docking studies and toxicology prediction of isoquinoline derivatives as leucine aminopeptidase inhibitors, Chem. Pap. 71 (2017), pp. 2557–2568. doi:10.1007/s11696-017-0251-3.
  • N. Faraji, T. Zebardast, A. Zarghi, and Z. Hajimahdi, QSAR modeling of aminopeptidase N/CD13 (APN) inhibitory activity of some leucine ureido derivatives by GA-MLR and SW-MLR methods, Lett. Drug. Des. Discov. 14 (2017), pp. 1348–1357. doi:10.2174/1570180814666170529084557.
  • O. Farsa, J. Kana, I. Macko, J. Zelazkova, J. Podlipna, A. Cirkva, J. Maxa, and K. Stastnv, Synthesis and aminopeptidase N inhibiting activity of 3-(nitrophenoxymethyl)-[1,3,2]dioxaborolan-2-ols and their open analogues, Acta Pol. Pharm. 74 (2017), pp. 127–135.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.