Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors

European Journal of Medicinal Chemistry

Volumn 90, Issue , 2015, Pages 315-331

  Li, Rongshi ^a,b,c   Cheng, Chunwei ^d   Balasis, Maria E ^b   Liu, Yan ^a   Garner, Thomas P ^e   Daniel, Kenyon G ^b   Li, Jerry ^b   Qin, Yong ^d   Gavathiotis, Evripidis ^e   Sebti, Said M ^b,c  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF SOUTH FLORIDA   (United States)

^d SICHUAN UNIVERSITY   (China)

^e ALBERT EINSTEIN CANCER CENTER   (United States)

Author keywords

Apoptosis; Marinopyrroles; Mcl 1 and Bcl xL antagonists; Proteineprotein interaction

Indexed keywords

(1' TOSYL 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((METHOXY 4 ((TRIMETHYLSILYL)ETHYNYL)PHENYL)METHENONE); (2 (HYDROXY(2 METHOXY 4 METHYLPHENYL)METHYL) 1' TOSYL 1' H 1,3' BIPYRROL 2' YL) (2 METHOXY 4 METHYLPHENYL)METHANONE; (2 (HYDROXYMETHYL) 1' TOSYL-1' H 1,3' BYPYRROL 2' YL) (2 METHOXY 4 METHYLPHENYL)METHANONE; (4,4' 5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((2 HYDROXY 4 VINYLPHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((4 ETHYL 2 HYDROXYPHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((4 ETHYNYL 2 HYDROXYPHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((5 CHLORO 2 HYDROXY 4 METHYLPHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((5 CHLORO 2 METHOXY 4METHYLPHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' TOSYL 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((2 HYDROXY 4 ((TRIMETHYLSILYL)ETHYNYL)PHENYL)METHANONE); (4,4' 5,5' TETRACHLORO 1' TOSYL 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((2 METHOXY 4 ((TRIMETHYLSILYL)ETHYNYL)PHENYL)METHANONE); (4,4',5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DIYL)BIS((4 (1 BENZYL 1H 1,2,3 TRIAZOL 5 YL) 2 HYDROXYPHENYL)METHANONE); 1' H 1,3' BIPYRROLE 2,2' DIYLBIS((2 METHOXY 4 METHYLPHENYL); 1' H 1,3' BIPYRROLE 2,2' DIYLBIS((4 ETHYNYL 2 HYDROXYPHENYL)METHANONE); 1' H 1,3' BIPYRROLE 2,2' DIYLBIS((4 ETHYNYL 2 METHOXYPHENYL)METHANONE); 2' (2 METHOXY 4 METHYLBENZOYL) 1' TOSYL 1'H 1,3' BYPYRROLE 2 CARBALDEHYDE; 2,2' (4,4' ((4,4'5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DICARBONYL)BIS(2 CHLORO 5 HYDROXY 4,1 PHENYLENE))BIS(1H 1,2,3 TRIAZOLE 4,1 DIYL))DIACETIC ACID; ANTINEOPLASTIC AGENT; BH3 PROTEIN; BIM PROTEIN; DI TERT BUTYL 2,2'(4,4' ((4,4',5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DICARBONYL)BIS(2 CHLORO 5 HYDROXY 4,1 PHENYLENE))BIS(1H 1,2,3 TRIAZOLE 4,1 DIYL))DIACETATE; DIETHYL 2,2' (4,4' ((1' H 1,3' BIPYRROLE 2,2' DICARBONYL)BIS(3 METHOXY 4,1 PHENYLENE))BIS(1H 1,2,3 TRIAZOLE 4,1 DIYL)DIACETATE; DIETHYL 2,2' (4,4' ((4,4'5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DICARBONYL)BIS(2 CHLORO 5 HYDROXY 4,1 PHENYLENE))BIS(1H 1,2,3 TRIAZOLE 4,1 DIYL)DIACETATE; DIETHYL 2,2' [4,4' [(4,4'5,5' TETRACHLORO 1' H 1,3' BIPYRROLE 2,2' DICARBONYL)BIS(2 CHLORO 5 METHOXY 4,1 PHENYLENE)]BIS(1H 1,2,3 TRIAZOLE 4,1 DIYL)]DIACETATE; MARINOPYRROLE DERIVATIVE; PROTEIN BCL XL; PROTEIN INHIBITOR; PROTEIN MCL 1; UNCLASSIFIED DRUG; [2 [[(TERT BUTYLDIMETHYLSILYL)OXY]METHYL] 1' TOSYL 1' H 1,3' BIPYRROL 2' YL] (2 METHOXY 4 METHYLPHENYL)METHANOL; [2 [[(TERT BUTYLDIMETHYLSILYL)OXY]METHYL] 1' TOSYL 1' H 1,3' BIPYRROL 2' YL] (2 METHOXY 4 METHYLPHENYL)METHANONE; APOPTOSIS REGULATORY PROTEIN; MARINOPYRROLE A; MCL1 PROTEIN, HUMAN; PROTEIN BCL X; PYRROLE DERIVATIVE;

APOPTOSIS; ARTICLE; BINDING SITE; BREAST CANCER; CANCER CELL; CANCER RESISTANCE; CARBON NUCLEAR MAGNETIC RESONANCE; DRUG DESIGN; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MOLECULAR DOCKING; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; METABOLISM; SYNTHESIS;

APOPTOSIS REGULATORY PROTEINS; BCL-X PROTEIN; BINDING SITES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; MOLECULAR STRUCTURE; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PYRROLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84947617221     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.11.035     Document Type: Article

References (52)

1. N.N. Danial, S.J. Korsmeyer, Cell death: critical control points, Cell 116 (2004) 205e219.
2. Y. Fuchs, H. Steller, Programmed cell death in animal development and disease, Cell 147 (2011) 742e758.
3. D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation, Cell 144 (2011) 646e674.
4. G.L. Kelly, A. Strasser, The essential role of evasion from cell death in cancer, Adv. Canc. Res. 111 (2011) 39e96.
5. R.J. Youle, A. Strasser, The BCL-2 protein family: opposing activities that mediate cell death, Nat. Rev. Mol. Cell. Biol. 9 (2008) 47e59.
6. J.E. Chipuk, T. Moldoveanu, F. Llambi, M.J. Parsons, D.R. Green, The BCL-2 family reunion, Mol. Cell. 37 (2010) 299e310.
7. T. Moldoveanu, A.V. Follis, R.W. Kriwacki, D.R. Green, Many players in BCL-2 family affairs, Trends Bioch. Sci. 39 (2014) 101e111.
8. F. Llambi, D.R. Green, Apoptosis and oncogenesis: give and take in the BCL-2 family, Curr. Opin. Gen. Dev. 21 (2011) 12e20.
9. A. Strasser, S. Cory, J.M. Adams, Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases, EMBO J. 30 (2011) 3667e3683.
10. P.N. Kelly, A. Strasser, The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy, Cell. Death Diff 18 (2011) 1414e1424.
11. J.A. Wells, C.L. McClendon, Reaching for high-hanging fruit in drug discovery at protein-protein interfaces, Nature 450 (2007) 1001e1009.
12. C. Billard, BH3 mimetics: status of the field and new developments, Mol. Cancer Ther. 12 (2013) 1691e1700.
13. C. Tse, A.R. Shoemaker, J. Adickes, M.G. Anderson, J. Chen, S. Jin, E.F. Johnson, K.C. Marsh, M.J. Mitten, P. Nimmer, L. Roberts, S.K. Tahir, Y. Xiao, X. Yang, H. Zhang, S. Fesik, S.H. Rosenberg, S.W. Elmore, ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor, Cancer Res. 68 (2008) 3421e3428.
14. A.J. Souers, J.D. Leverson, E.R. Boghaert, S.L. Ackler, N.D. Catron, J. Chen, B.D. Dayton, H. Ding, S.H. Enschede, W.J. Fairbrother, D.C. Huang, S.G. Hymowitz, S. Jin, S.L. Khaw, P.J. Kovar, L.T. Lam, J. Lee, H.L. Maecker, K.C. Marsh, K.D. Mason, M.J. Mitten, P.M. Nimmer, A. Oleksijew, C.H. Park, C.M. Park, D.C. Phillips, A.W. Roberts, D. Sampath, J.F. Seymour, M.L. Smith, G.M. Sullivan, S.K. Tahir, C. Tse, M.D. Wendt, Y. Xiao, J.C. Xue, H. Zhang, R.A. Humerickhouse, S.H. Rosenberg, S.W. Elmore, ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets, Nat. Med. 19 (2013) 202e208.
15. T. Oltersdorf, S.W. Elmore, A.R. Shoemaker, R.C. Armstrong, D.J. Augeri, B.A. Belli, M. Bruncko, T.L. Deckwerth, J. Dinges, P.J. Hajduk, M.K. Joseph, S. Kitada, S.J. Korsmeyer, A.R. Kunzer, A. Letai, C. Li, M.J. Mitten, D.G. Nettesheim, S. Ng, P.M. Nimmer, J.M. O'Connor, A. Oleksijew, A.M. Petros, J.C. Reed, W. Shen, S.K. Tahir, C.B. Thompson, K.J. Tomaselli, B. Wang, M.D. Wendt, H. Zhang, S.W. Fesik, S.H. Rosenberg, An inhibitor of Bcl-2 family proteins induces regression of solid tumours, Nature 435 (2005) 677e681.
16. M. Konopleva, R. Contractor, T. Tsao, I. Samudio, P.P. Ruvolo, S. Kitada, X. Deng, D. Zhai, Y.X. Shi, T. Sneed, M. Verhaegen, M. Soengas, V.R. Ruvolo, T. McQueen, W.D. Schober, J.C. Watt, T. Jiffar, X. Ling, F.C. Marini, D. Harris, M. Dietrich, Z. Estrov, J. McCubrey, W.S. May, J.C. Reed, M. Andreeff, Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia, Cancer Cell. 10 (2006) 375e388.
17. M.F. van Delft, A.H. Wei, K.D. Mason, C.J. Vandenberg, L. Chen, P.E. Czabotar, S.N. Willis, C.L. Scott, C.L. Day, S. Cory, J.M. Adams, A.W. Roberts, D.C. Huang, The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized, Cancer Cell. 10 (2006) 389e399.
18. X. Lin, S. Morgan-Lappe, X. Huang, L. Li, D.M. Zakula, L.A. Vernetti, S.W. Fesik, Y. Shen, 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737, Oncogene 26 (2007) 3972e3979.
19. P. Gomez-Bougie, S. Wuilleme-Toumi, E. Menoret, V. Trichet, N. Robillard, M. Philippe, R. Bataille, M. Amiot, Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma, Cancer Res. 67 (2007) 5418e5424.
20. C. Akgul, Mcl-1 is a potential therapeutic target in multiple types of cancer, Cell. Mol. life Sci. CMLS 66 (2009) 1326e1336.
21. M.L. Stewart, E. Fire, A.E. Keating, L.D. Walensky, The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer, Nat. Chem. Biol. 6 (2010) 595e601.
22. P.H. Bernardo, T. Sivaraman, K.F. Wan, J. Xu, J. Krishnamoorthy, C.M. Song, L. Tian, J.S. Chin, D.S. Lim, H.Y. Mok, V.C. Yu, J.C. Tong, C.L. Chai, Structural insights into the design of small molecule inhibitors that selectively antagonize Mcl-1, J. Med. Chem. 53 (2010) 2314e2318.
23. R. Dash, B. Azab, B.A. Quinn, X. Shen, X.Y. Wang, S.K. Das, M. Rahmani, J. Wei, M. Hedvat, P. Dent, I.P. Dmitriev, D.T. Curiel, S. Grant, B. Wu, J.L. Stebbins, M. Pellecchia, J.C. Reed, D. Sarkar, P.B. Fisher, Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity, PNAS 108 (2011) 8785e8790.
24. A. Muppidi, K. Doi, S. Edwardraja, E.J. Drake, A.M. Gulick, H.G. Wang, Q. Lin, Rational design of proteolytically stable, cell-permeable peptide-based selective Mcl-1 inhibitors, J. Am. Chem. Soc. 134 (2012) 14734e14737.
25. K. Doi, R. Li, S.S. Sung, H. Wu, Y. Liu, W. Manieri, G. Krishnegowda, A. Awwad, A. Dewey, X. Liu, S. Amin, C. Cheng, Y. Qin, E. Schonbrunn, G. Daughdrill, T.P. Loughran Jr., S. Sebti, H.G. Wang, Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation, J. Boil. Chem. 287 (2012) 10224e10235.
26. N.A. Cohen, M.L. Stewart, E. Gavathiotis, J.L. Tepper, S.R. Bruekner, B. Koss, J.T. Opferman, L.D. Walensky, A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival, Chem. Biol. 19 (2012) 1175e1186.
27. Y. Tanaka, K. Aikawa, G. Nishida, M. Homma, S. Sogabe, S. Igaki, Y. Hayano, T. Sameshima, I. Miyahisa, T. Kawamoto, M. Tawada, Y. Imai, M. Inazuka, N. Cho, Y. Imaeda, T. Ishikawa, Discovery of potent Mcl-1/Bcl-xL dual inhibitors by using a hybridization strategy based on structural analysis of target proteins, J. Med. Chem. 56 (2013) 9635e9645.
28. A. Friberg, D. Vigil, B. Zhao, R.N. Daniels, J.P. Burke, P.M. Garcia-Barrantes, D. Camper, B.A. Chauder, T. Lee, E.T. Olejniczak, S.W. Fesik, Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design, J. Med. Chem. 56 (2013) 15e30.
29. F.A. Abulwerdi, C. Liao, A.S. Mady, J. Gavin, C. Shen, T. Cierpicki, J.A. Stuckey, H.D. Showalter, Z. Nikolovska-Coleska, 3-Substituted-N-(4-hydroxynaphthalen-1-yl)arylsulfonamides as a novel class of selective Mcl-1 inhibitors: structure-based design, synthesis, SAR, and biological evaluation, J. Med. Chem. 57 (2014) 4111e4133.
30. F. Abulwerdi, C. Liao, M. Liu, A.S. Azmi, A. Aboukameel, A.S. Mady, T. Gulappa, T. Cierpicki, S. Owens, T. Zhang, D. Sun, J.A. Stuckey, R.M. Mohammad, Z. Nikolovska-Coleska, A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo, Mol. Cancer Ther. 13 (2014) 565e575.
31. C. Cheng, Y. Liu, M.E. Balasis, T.P. Garner, J. Li, N.L. Simmons, N. Berndt, H. Song, L. Pan, Y. Qin, K.C. Nicolaou, E. Gavathiotis, S.M. Sebti, R. Li, Marinopyrrole derivatives with sulfide spacers as selective disruptors of mcl-1 binding to pro-apoptotic protein bim, Mar. Drugs 12 (2014) 4311e4325.
32. E. Fire, S.V. Gulla, R.A. Grant, A.E. Keating, Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes, Protein Sci. 19 (2010) 507e519.
33. S. Dutta, S. Gulla, T.S. Chen, E. Fire, R.A. Grant, A.E. Keating, Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL, J. Mol. Biol. 398 (2010) 747e762.
34. G.W. Foight, J.A. Ryan, S.V. Gulla, A. Letai, A.E. Keating, Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells, ACS Chem. Biol. (2014), http://dx.doi.org/10.1021/cb500340w.
35. C. Cheng, Y. Liu, H. Song, L. Pan, J. Li, Y. Qin, R. Li, Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (II), Mar. Drugs 11 (2013) 2927e2948.
36. C. Cheng, L. Pan, Y. Chen, H. Song, Y. Qin, R. Li, Total synthesis of (±)-marinopyrrole A and its library as potential antibiotic and anticancer agents, J. Comb. Chem. 12 (2010) 541e547.
37. H.C. Kolb, M.G. Finn, K.B. Sharpless, Click chemistry: diverse chemical function from a few good reactions, Angew. Chem. 40 (2001) 2004e2021.
38. Q. Liu, T. Moldoveanu, T. Sprules, E. Matta-Camacho, N. Mansur-Azzam, K. Gehring, Apoptotic regulation by MCL-1 through heterodimerization, J. Biol. Chem. 285 (2010) 19615e19624.
39. Y. Liu, N.M. Haste, W. Thienphrapa, V. Nizet, M. Hensler, R. Li, Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I), Mar. Drugs 10 (2012) 953e962.
40. C. Cheng, Y. Liu, M.E. Balasis, N.L. Simmons, J. Li, H. Song, L. Pan, Y. Qin, K.C. Nicolaou, S.M. Sebti, R. Li, Cyclic marinopyrrole derivatives as disruptors of Mcl-1 and Bcl-x(L) binding to Bim, Mar. Drugs 12 (2014) 1335e1348.
41. Y. Liu, N.M. Haste, W. Thienphrapa, J. Li, V. Nizet, M. Hensler, R. Li, Marinopyrrole derivatives as potential antibiotic agents against methicillinresistant Staphylococcus aureus (III), Mar. Drugs 12 (2014) 2458e2470.
42. T.S. Chen, H. Palacios, A.E. Keating, Structure-based redesign of the binding specificity of anti-apoptotic Bcl-x(L), J. Mol. Biol. 425 (2013) 171e185.
43. W.F. Vranken, W. Boucher, T.J. Stevens, R.H. Fogh, A. Pajon, M. Llinas, E.L. Ulrich, J.L. Markley, J. Ionides, E.D. Laue, The CCPN data model for NMR spectroscopy: development of a software pipeline, Proteins 59 (2005) 687e696.
44. R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis, P.S. Shenkin, Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy, J. Med. Chem. 47 (2004) 1739e1749.
45. T.A. Halgren, R.B. Murphy, R.A. Friesner, H.S. Beard, L.L. Frye, W.T. Pollard, J.L. Banks, Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening, J. Med. Chem. 47 (2004) 1750e1759.
46. R.A. Friesner, R.B. Murphy, M.P. Repasky, L.L. Frye, J.R. Greenwood, T.A. Halgren, P.C. Sanschagrin, D.T. Mainz, Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes, J. Med. Chem. 49 (2006) 6177e6196.
47. E. Gavathiotis, D.E. Reyna, J.A. Bellairs, E.S. Leshchiner, L.D. Walensky, Direct and selective small-molecule activation of proapoptotic BAX, Nat. Chem. Biol. 8 (2012) 639e645.
48. J.R. Greenwood, D. Calkins, A.P. Sullivan, J.C. Shelley, Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution, J. Comp. Mol. Des. 24 (2010) 591e604.
49. J.C. Shelley, A. Cholleti, L.L. Frye, J.R. Greenwood, M.R. Timlin, M. Uchimaya, Epik: a software program for pK(a) prediction and protonation state generation for drug-like molecules, J. Comp. Mol. Des. 21 (2007) 681e691.
50. R. Abel, N.K. Salam, J. Shelley, R. Farid, R.A. Friesner, W. Sherman, Contribution of explicit solvent effects to the binding affinity of small-molecule inhibitors in blood coagulation factor serine proteases, ChemMedChem 6 (2011) 1049e1066.
51. Maestro, Version 9.7, Schrodinger, LLC, New York, NY, 2014.
52. The PyMOL Molecular Graphics System. Version 1.4, Schrodinger, LLC, New York, 2011.