Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1)*

David J. A. Bridewell; Jonathan Sperry; Jason R. Smith; Priambudi Kosim-Satyaputra; Lai-Ming Ching; Joanne F. Jamie; Margaret A. Brimble

doi:10.1071/CH12393

RESEARCH ARTICLE

Natural Product-Inspired Pyranonaphthoquinone Inhibitors of Indoleamine 2,3-Dioxygenase-1 (IDO-1)*

David J. A. Bridewell ^A , Jonathan Sperry ^B , Jason R. Smith ^C , Priambudi Kosim-Satyaputra ^C , Lai-Ming Ching ^A , Joanne F. Jamie ^C and Margaret A. Brimble ^B ^D

+ Author Affiliations

- Author Affiliations

^A Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland Central 1010, New Zealand.

^B School of Chemical Sciences, The University of Auckland, Auckland Central 1010, New Zealand.

^C Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.

^D Corresponding author. Email: m.brimble@auckland.ac.nz

Australian Journal of Chemistry 66(1) 40-49 https://doi.org/10.1071/CH12393
Submitted: 23 August 2012 Accepted: 29 October 2012 Published: 12 November 2012

Abstract

A series of pyranonaphthoquinone derivatives possessing structural features present in both natural products annulin B and exiguamine A have been shown to exhibit low micromolar inhibition of indoleamine 2,3-dioxygenase-1 (IDO-1). These inhibitors retain activity against the enzyme in a cellular context with an approximate one-log loss of dose potency against IDO-1 in cells. One particular analogue, triazole 8 shows good inhibition of IDO-1 along with little loss of cell viability at low drug concentrations. These results have extended the naphthoquinone series of novel IDO-1 inhibitors based on lead compounds from nature.

References

[1] K. Higuchi, S. Kuno, O. Hayaishi, Fed. Proc. 1963, 22, 243.(abstr.)

[2] K. Higuchi, O. Hayaishi, Arch. Biochem. Biophys. 1967, 120, 397.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2sXktVyju7w%3D&md5=cc86740cee84e232c1481e4e7157e7f7CAS |

[3] T. Shimizu, S. Nomiyama, F. Hirata, O. Hayaishi, J. Biol. Chem. 1978, 253, 4700.
| 1:CAS:528:DyaE1cXkvVKgtrc%3D&md5=3f8572999185e688d734220090af5536CAS |

[4] O. Takikawa, R. Yoshida, R. Kido, O. Hayaishi, J. Biol. Chem. 1986, 261, 3648.
| 1:CAS:528:DyaL28XitVCnsrs%3D&md5=73ea2821462142b1d97202d52a21531aCAS |

[5] D. H. Munn, E. Shafizadeh, J. T. Attwood, I. Bondarev, A. Pashine, A. L. Mellor, J. Exp. Med. 1999, 189, 1363.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXivFGku7w%3D&md5=364d820b7d974dfe48f79d0623fc79b8CAS |

[6] D. H. Munn, M. Zhou, J. T. Attwood, Science 1998, 281, 1191.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXls1Cqu7c%3D&md5=88f8bd1396afd01fbb8bd513158001f3CAS |

[7] G. J. Guillemin, B. J. Brew, C. E. Noonan, O. Takikawa, K. M. Cullen, Neuropathol. Appl. Neurobiol. 2005, 31, 395.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpslWisr8%3D&md5=2bc57ea5eeabd3477b37744117a59256CAS |

[8] T. Hayashi, L. Beck, C. Rossetto, X. Gong, O. Takikawa, K. Takabayashi, D. H. Broide, D. A. Carson, E. Raz, J. Clin. Invest. 2004, 114, 270.
| 1:CAS:528:DC%2BD2cXlvFWmsbs%3D&md5=8a4bb449f2121efefc5f516a0c83e070CAS |

[9] R. Potula, L. Poluektova, B. Knipe, J. Chrastil, D. Heilman, H. Dou, O. Takikawa, D. H. Munn, H. E. Gendelman, P. Persidsky, Blood 2005, 106, 2382.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVKqt7zJ&md5=4c68dd5484777317e9476bea778bf869CAS |

[10] O. Takikawa, R. J. Truscott, M. Fukao, S. Miwa, Adv. Exp. Med. Biol. 2003, 527, 277.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXktlOjtrw%3D&md5=409f1d1a9a8f9b2edb7a6642e12659bcCAS |

[11] M. C. Wichers, M. J. Maes, J. Psychiatry Neurosci. 2004, 29, 11.

[12] A. J. Muller, G. C. Prendergast, Cancer Res. 2005, 65, 8065.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVShsb3E&md5=ed7a4d26147122e93864ac681723972bCAS |

[13] A. J. Muller, W. P. Malachowski, G. C. Prendergast, Expert Opin. Ther. Targets 2005, 9, 831.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmvFels7k%3D&md5=17563065d2397960ccff3072351fa95dCAS |

[14] C. Uyttenhove, L. Pilotte, I. Theate, V. Stroobant, D. Colau, N. Parmentier, T. Boon, B. van den Eynde, Nat. Med. 2003, 9, 1269.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXns1Clu7c%3D&md5=32b2544ce11dbf4ec0e5dd596134b217CAS |

[15] J. B. Katz, A. J. Muller, G. C. Prendergast, Immunol. Rev. 2008, 222, 206.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsFejt70%3D&md5=9bd871c57c23a127d8d40cc2035e0a0fCAS |

[16] G. C. Prendergast, Oncogene 2008, 27, 3889.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXns1OnsrY%3D&md5=16419bf7b822ccd87fb8b51de27a274cCAS |

[17] A. J. Muller, P. A. Scherle, Natl. Rev. 2006, 6, 613.
| 1:CAS:528:DC%2BD28XntFGlu7s%3D&md5=0e8701d8409f2dd6620116e60272ecb1CAS |

[18] A. Macchiarulo, E. Camiaoni, R. Nuti, R. Pellicciari, Amino Acids 2009, 37, 219.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXotVKju7s%3D&md5=83c0f06efde73e6867bcb7f7d33c02f1CAS |

[19] X. Zheng, J. Koropatnick, M. Li, X. Zhang, F. Ling, X. Ren, X. Hao, H. Sun, C. Vladau, J. A. Franek, B. Feng, B. L. Urquhart, R. Zhong, D. J. Freeman, B. Garcia, W. P. Min, J. Immunol. 2006, 177, 5639.
| 1:CAS:528:DC%2BD28XhtVans7%2FM&md5=f1f0808271e863b29ecb0bd6bb5eb126CAS |

[20] A. J. Muller, J. B. Duhadaway, P. S. Donover, E. Sutanto-Ward, G. C. Prendergast, Nat. Med. 2005, 11, 312.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhvVSru7c%3D&md5=7848d37526f640e1881cb4b17604ac55CAS |

[21] T. Banerjee, J. B. Duhadaway, P. Gaspari, E. Sutanto-Ward, D. H. Munn, A. L. Mellor, W. P. Malachowski, G. C. Prendergast, A. J. Muller, Oncogene 2008, 27, 2851.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXltlSgsr0%3D&md5=a35e1414025f40ace8d4b1beffb67f07CAS |

[22] S. Kumar, W. P. Malachowski, J. B. DuHadaway, J. M. LaLonde, P. J. Carroll, D. Jaller, R. Metz, G. C. Prendergast, A. J. Muller, J. Med. Chem. 2008, 51, 1706.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXislKqtL4%3D&md5=3c324c27f3d3e25d8fbc4e318ab3d573CAS |

[23] Y. Watanabe, F. Motokazu, H. Osamu, T. Tomio, U. Hamao, Biochem. Biophys. Res. Commun. 1978, 85, 273.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1MXltVCrug%3D%3D&md5=73c3d543d9a61246343303f5ee7d16bbCAS |

[24] S. G. Cady, M. Sono, Arch. Biochem. Biophys. 1991, 291, 326.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XhtVWmu78%3D&md5=d4df4f6d198c972a51b88ad0dedab0ebCAS |

[25] M. Sono, S. G. Cady, Biochemistry 1989, 28, 5392.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXktF2qtLg%3D&md5=681786fc2063386ac731f0082829ee75CAS |

[26] N. Eguchi, Y. Watanabe, K. Kawanishi, Y. Hashimoto, O. Hayaishi, Arch. Biochem. Biophys. 1984, 232, 602.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXlsVKltro%3D&md5=f550e03cb72f8243d64340544ecc79e5CAS |

[27] A. C. Peterson, A. J. La Loggia, L. K. Hamaker, R. A. Arend, P. L. Fisette, Y. Ozaki, J. A. Will, R. R. Brown, J. M. Cook, Med. Chem. Res. 1993, 7, 473.

[28] H. Sugimoto, S. Oda, T. Otsuki, T. Hino, T. Yoshida, Y. Shiro, Proc. Natl. Acad. Sci. USA 2006, 103, 2611.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XksF2rsb4%3D&md5=786720ae26e106637fa6974b70149948CAS |

[29] S. Kumar, D. Jaller, B. Patel, J. M. LaLonde, J. B. DuHadaway, W. P. Malachowski, G. C. Prendergast, A. J. Muller, J. Med. Chem. 2008, 51, 4968.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXptVyrtrY%3D&md5=c80bd2c1b95ecf58d85900634769289eCAS |

[30] H. Nakashima, Y. Uto, E. Nakata, H. Nagasawa, K. Ikkyu, N. Hiraoka, K. Nakashima, Y. Sasaki, H. Sugimoto, Y. Shiro, T. Hashimoto, Y. Okamoto, Y. Asakawa, H. Hori, Bioorg. Med. Chem. 2008, 16, 8661.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFantLjK&md5=88322fc8a26e796cff0018e505cb4759CAS |

[31] H. Nakashima, K. Ikkyu, K. Nakashima, K. Sano, Y. Uto, E. Nakata, H. Nagasawa, H. Sugimoto, Y. Shiro, Y. Nakagawa, H. Hori, Adv. Exp. Med. Biol. 2010, 662, 415.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1Wmsr%2FL&md5=c7368e79cb5ebbf3fdb76189f8b6023fCAS |

[32] E. Dolušić, P. Larrieu, S. Blanc, F. Sapunaric, B. Norberg, L. Moineaux, D. Colette, V. Stroobant, L. Pilotte, D. Colau, T. Ferain, G. Fraser, M. Galeni, J.-M. Frère, B. Masereel, B. van den Eynde, J. Wouters, R. Frédérick, Bioorg. Med. Chem. 2011, 19, 1550.
| Crossref | GoogleScholarGoogle Scholar |

[33] E. Dolušić, P. Larrieu, S. Blanc, F. Sapunaric, J. Pouyez, L. Moineaux, D. Colette, V. Stroobant, L. Pilotte, D. Colau, T. Ferain, G. Fraser, M. Galleni, J.-M. Frere, B. Masereel, B. van den Eynde, J. Wouters, R. Frederick, Eur. J. Med. Chem. 2011, 46, 3058.
| Crossref | GoogleScholarGoogle Scholar |

[34] K. Matsuno, K. Takai, Y. Isaka, Y. Unno, M. Sato, O. Takikawa, A. Asai, Bioorg. Med. Chem. Lett. 2010, 20, 5126.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVehsbfE&md5=14903238dedada29abe24aa8a309e051CAS |

[35] E. W. Yue, B. Douty, B. Wayland, M. Bower, X. Liu, L. Leffet, Q. Wang, K. J. Bowman, M. J. Hansbury, C. Liu, M. Wei, Y. Li, R. Wynn, T. C. Burn, H. K. Koblish, J. S. Fridman, B. Metcalf, P. A. Scherle, A. P. Combs, J. Med. Chem. 2009, 52, 7364.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXntVSksb8%3D&md5=a911bbb5810a2486bd7a0c0720946ec1CAS |

[36] H. K. Koblish, M. J. Hansbury, K. J. Bowman, G. Yang, C. L. Neilan, P. J. Haley, T. C. Burn, P. Waeltz, R. B. Sparks, E. W. Yue, A. P. Combs, P. A. Scherle, K. Vaddi, J. S. Fridman, Mol. Cancer Ther. 2010, 9, 489.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhslersrY%3D&md5=ce08f652df240ebbe736829152223913CAS |

[37] E. Vottero, A. Balgi, K. Woods, S. Tugendreich, T. Melese, R. J. Andersen, A. G. Mauk, M. Roberge, Biotechnol. J. 2006, 1, 282.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XmtlKqtbs%3D&md5=8acad6aba14afc14e95d1002a54e2f6fCAS |

[38] A. C. Terentis, M. Freewan, T. S. Sempertegui Plaza, M. J. Raftery, R. Stocker, S. R. Thomas, Biochemistry 2010, 49, 591.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhs1Smsb3K&md5=c3e9843104d62a2ad3fda46f7e2fe626CAS |

[39] (a) Q. Huang, M. Zheng, S. Yang, C. Kuang, C. Yu, Q. Yang, Eur. J. Med. Chem. 2011, 46, 5680.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlKkurvL&md5=4fb6b8f81e0fd57d6a08721e992ac33dCAS |
      (b) F. U. Röhrig, S. R. Majjigapu, A. Grosdidier, S. Bron, V. Stroobant, L. Pilotte, D. Colau, P. Vogel, B. J. Van den Eynde, V. Zoete, O. Michielin, J. Med. Chem. 2012, 55, 5270.
         | Crossref | GoogleScholarGoogle Scholar |

[40] (a) U. F. Röhrig, L. Awad, A. Grosdidier, P. Larrieu, V. Stroobant, D. Colau, V. Cerundolo, A. J. Simpson, P. Vogel, B. J. van den Eynde, V. Zoete, O. Michielin, J. Med. Chem. 2010, 53, 1172.
         | Crossref | GoogleScholarGoogle Scholar |
      (b) S. John, S. Thangapandian, S. Sakkiah, K. W. Lee, Eur. J. Med. Chem. 2010, 45, 4004.
         | Crossref | GoogleScholarGoogle Scholar |

[41] P. Gaspari, T. Banerjee, W. P. Malachowski, A. J. Muller, G. C. Prendergast, J. DuHadaway, S. Bennett, A. M. Donovan, J. Med. Chem. 2006, 49, 684.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtlWmurfN&md5=340e20037e6f2099c9823749c08960c2CAS |

[42] H. C. Brastianos, E. Vottero, B. O. Patrick, R. Van Soest, T. Matainaho, A. G. Mauk, R. J. Andersen, J. Am. Chem. Soc. 2006, 128, 16046.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtlCgsrbO&md5=fb105dd3a280b47ed2a1665a6d02e2adCAS |

[43] G. Carr, M. K. Chung, A. G. Mauk, R. J. Andersen, J. Med. Chem. 2008, 51, 2634.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktlCit7Y%3D&md5=8107907174856adf989fb79b86339736CAS |

[44] M. Volgraf, J.-P. Lumb, H. C. Brastianos, G. Carr, M. K. W. Chung, M. Muenzel, A. G. Mauk, R. J. Andersen, D. Trauner, Nat. Chem. Biol. 2008, 4, 535.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXpvFGrtLo%3D&md5=2a3b1bb99032b55341ff92edb44284a5CAS |

[45] G. Carr, W. Tay, H. Bottriell, S. K. Andersen, G. A. Mauk, R. J. Andersen, Org. Lett. 2009, 11, 2996.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnsVOmtLw%3D&md5=1c2d5b327a5fb1facb5c58e31916729dCAS |

[46] A. Pereira, E. Vottero, M. Roberge, A. G. Mauk, R. J. Andersen, J. Nat. Prod. 2006, 69, 1496.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVShs7nI&md5=a2bcd274634c53cfe179a733ed4f9c62CAS |

[47] E. Fahy, R. J. Andersen, C. Xu, J. Clardy, J. Org. Chem. 1986, 51, 5145.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXjtVGn&md5=25abe26991ec0177cccd3a3503e31a57CAS |

[48] J. Sperry, P. Bachu, M. A. Brimble, Nat. Prod. Rep. 2008, 25, 376.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXkt1Sms7g%3D&md5=cfff6e81b84af3f63fcbd7ec8ba9971eCAS |

[49] J. Sperry, I. Lorenzo-Castrillejo, M. A. Brimble, F. Machín, Bioorg. Med. Chem. 2009, 17, 7131.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht1ais7vL&md5=d147a1617af3b56d16d9ea2994748791CAS |

[50] K. Rathwell, J. Sperry, M. A. Brimble, Tetrahedron 2010, 66, 4002.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmtFyrtr8%3D&md5=196d17c5d653e6c7bdc14c738ef3b512CAS |

[51] J. S. Gibson, O. Andrey, M. A. Brimble, Synthesis 2007, 2611.
| 1:CAS:528:DC%2BD2sXhtVKls7%2FN&md5=f47ba938779647f7a664b589225f2d51CAS |

[52] P. Bachu, J. Sperry, M. A. Brimble, Tetrahedron 2008, 64, 4827.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlvVWgsL4%3D&md5=0fb097f6fd6149eec56579afaa92d0dcCAS |

[53] J. Sperry, J. J. P. Sejberg, F. M. Stiemke, M. A. Brimble, Org. Biomol. Chem. 2009, 7, 2599.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnvV2nsbY%3D&md5=03795d8685d46f06ad1e2c282b671cc0CAS |

[54] P. Bachu, J. Sperry, M. A. Brimble, Tetrahedron 2008, 64, 3343.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXis1Clsro%3D&md5=562758c8dda50157afdc138df47a2c57CAS |

[55] M. A. Brimble, P. Bachu, J. Sperry, Synthesis 2007, 2887.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1KqsL7F&md5=3f4c3e2d06377d1c35bb87e945b43656CAS |

[56] J. Sperry, J. S. Gibson, J. J. P. Sejberg, M. A. Brimble, Org. Biomol. Chem. 2008, 6, 4261.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlWjt7nM&md5=faaac8c4b17fdb7a3e0275ecc28d8b08CAS |

[57] C. J. Austin, J. Mizdrak, A. Matin, N. Sirijovski, P. Kosim-Satyaputra, R. D. Willows, T. H. Roberts, R. J. Truscott, G. Polekhina, M. W. Parker, J. F. Jamie, Protein Expr. Purif. 2004, 37, 392.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnsFGgtL4%3D&md5=9b9f6cd64f1e228ae190413599e09190CAS |

[58] D. J. Bridewell, G. J. Finlay, B. C. Baguley, Oncol. Res. 1997, 9, 535.
| 1:CAS:528:DyaK1cXisVCntLk%3D&md5=797b28afcd1682a4038f21e27d299392CAS |

[59] D. J. Bridewell, A. C. Porter, G. J. Finlay, B. C. Baguley, Cancer Chemother. Pharmacol. 2008, 62, 753.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1CjtL3N&md5=6828b659a1f1ee4bfd39341f371e36efCAS |

[60] I. Efimov, J. Basran, X. Sun, N. Chauhan, S. K. Chapman, C. G. Mowat, E. L. Raven, J. Am. Chem. Soc. 2012, 134, 3034.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhs1ehsLk%3D&md5=e7cc6399e3f8764f23bfde6180f1bf11CAS |

[61] A. Haldane, K. M. Holdaway, G. J. Finlay, B. C. Baguley, Cancer Chemother. Pharmacol. 1993, 32, 463.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXhsFeisb4%3D&md5=29bd4883539aabe9d6f09e467286a785CAS |