Lathyrol diterpenes as modulators of P-glycoprotein dependent multidrug resistance: Structure-activity relationship studies on Euphorbia factor L3 derivatives

Journal of Medicinal Chemistry

Volumn 58, Issue 9, 2015, Pages 3720-3738

  Jiao, Wei ^a   Wan, Zhongmin ^a   Chen, Shuang ^a   Lu, Runhua ^b   Chen, Xiaozhen ^a   Fang, Dongmei ^a   Wang, Jiufeng ^a   Pu, Shengcai ^a   Huang, Xin ^a   Gao, Haixiang ^b   Shao, Huawu ^a  

^a CHENGDU INSTITUTE OF BIOLOGY   (China)

^b CHINA AGRICULTURAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

3,5 DI(1 NAPHTHYLACETYLOXY)LATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIACETOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIBENZOYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIBUTYRYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIHEXANOYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIPHENYLACETYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIPHENYLPROPIONYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 3,5 DIPROPIONYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 5 (1 NAPHTHYLACETYLOXY)LATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 ACETOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 BENZOYLOXY 3 PROPIONYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 5 BENZOYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 CINNAMOYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 HEXANOYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 ISOBUTYRYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 ISOVALERYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 NICOTINOYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 PHENYLACETYLOXY 3 PROPIONYLOXYLATHYRA 6 (17),12 DIEN 15 OL 14 ONE; 5 PHENYLACETYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 PHENYLPROPIONYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 PROPIONYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; 5 VALERYLOXYLATHYRA 6 (17),12 DIEN 3,15 DIOL 14 ONE; DITERPENE; DOXORUBICIN; EUPHORBIA EXTRACT; LATHYRA 6 (17),12 DIEN 3,5,15 TRIOL 14 ONE; LATHYROL DITERPENE; MULTIDRUG RESISTANCE PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; 3,5-DIBENZOYLOXYLATHYRA-6(17),12-DIEN-15-OL-14-ONE; 5-(1-NAPHTHYLACETYLOXY)-3-PROPIONYLOXYLATHYRA-6(17),12-DIEN-15-OL-14-ONE; ANTINEOPLASTIC AGENT;

ARTICLE; BREAST CANCER; CYTOTOXICITY ASSAY; EUPHORBIA; EUPHORBIA LATHYRIS; HUMAN; HUMAN CELL; HYDROGEN BOND; MOLECULAR DYNAMICS; STRUCTURE ACTIVITY RELATION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; CYTOLOGY; DRUG EFFECTS; DRUG RESISTANCE; ISOLATION AND PURIFICATION; MCF 7 CELL LINE; METABOLISM; MULTIDRUG RESISTANCE; STEREOISOMERISM; X RAY CRYSTALLOGRAPHY;

ANTINEOPLASTIC AGENTS; CRYSTALLOGRAPHY, X-RAY; DITERPENES; DOXORUBICIN; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; EUPHORBIA; MCF-7 CELLS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; P-GLYCOPROTEIN; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84929340110     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00058     Document Type: Article

References (58)

1. Latest world cancer statistics. Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed (press releases 2013 of International Agency for Research on Cancer, Dec 12, 2013). http://www.iarc.fr/en/media-centre/pr/2013/pdfs/pr223-E.pdf.
2. Li, Y.; Yuan, H.; Yang, K.; Xu, W.; Tang, W.; Li, X. The structure and functions of P-glycoprotein Curr. Med. Chem. 2010, 17, 786-800
3. Hortobagyi, G. N. Treatment of breast cancer N. Engl. J. Med. 1998, 339, 974-984
4. Longley, D. B.; Johnston, P. G. Molecular mechanisms of drug resistance J. Pathol. 2005, 205, 275-292
5. Gottesman, M. M.; Fojo, T.; Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters Nat. Rev. Cancer 2002, 2, 48-58
6. Eckford, P. D. W.; Sharom, F. J. ABC efflux pump-based resistance to chemotherapy drugs Chem. Rev. 2009, 109, 2989-3011
7. Mechetner, E.; Kyshtoobayeva, A.; Zonis, S.; Kim, H.; Stroup, R.; Garcia, R.; Parker, R. J.; Fruehauf, J. P. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin Clin. Cancer Res. 1998, 4, 389-98
8. Thiebaut, F.; Tsuruo, T.; Hamada, H.; Gottesman, M. M.; Pastan, I.; Willingham, M. C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 7735-7738
9. Edwards, J. E.; Alcorn, J.; Savolainen, J.; Anderson, B. D.; McNamara, P. J. Role of P-glycoprotein in distribution of nelfinavir across the blood-mammary tissue barrier and blood-brain barrier Antimicrob. Agents Chemother. 2005, 49, 1626-1628
10. Melaine, N.; Liénard, M. O.; Dorval, I.; Le Goascogne, C.; Lejeune, H.; Jégou, B. Multidrug resistance genes and p-glycoprotein in the testis of the rat, mouse, guinea pig, and human Biol. Reprod. 2002, 67 (6) 1699-1707
11. Saito, T.; Zhang, Z. J.; Ohtsubo, T.; Noda, I.; Shibamori, Y.; Yamamoto, T.; Saito, H. Homozygous disruption of the mdrla P-glycoprotein gene affects blood-nerve barrier function in mice administered with neurotoxic drugs Acta Otolaryngol. 2001, 121 (6) 735-742
12. Schinkel, A. H.; Jonker, J. W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview Adv. Drug Delivery Rev. 2003, 55, 3-29
13. Higgins, C. F.; Gottesman, M. M. Is the multidrug transporter a flippase? Trends Biochem. Sci. 1992, 17 (1) 18-21
14. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q.; Urbatsch, I. L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding Science 2009, 323, 1718-1722
15. Bruggemann, E. P.; Germann, U. A.; Gottesman, M. M.; Pastan, I. Two different regions of P-glycoprotein [corrected] are photoaffinity-labeled by azidopine J. Biol. Chem. 1989, 264, 15483-15488
16. Dey, S.; Ramachandra, M.; Pastan, I.; Gottesman, M. M. Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 10594-10599
17. Loo, T. W.; Clarke, D. M. Mutational analysis of ABC proteins Arch. Biochem. Biophys. 2008, 476, 51-64
18. Shi, Q. W.; Su, X. H.; Kiyota, H. Chemical and pharmacological research of the plants in genus Euphorbia Chem. Rev. 2008, 108, 4295-4327
19. Vasas, A.; Hohmann, J. Euphorbia diterpenes: isolation, structure, biological activity, and synthesis (2008-2012) Chem. Rev. 2014, 114, 8579-8612
20. Hohmann, J.; Molnár, J.; Rédei, D.; Evanics, F.; Forgo, P.; Kálmán, A. Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species J. Med. Chem. 2002, 45, 2425-2431
21. Hohmann, J.; Rédei, D.; Forgo, P.; Molnár, J.; Dombi, G.; Zorig, T. Jatrophane diterpenoids from Euphorbia mongolica as modulators of the multidrug resistance of L5128 mouse lymphoma cells J. Nat. Prod. 2003, 66, 976-979
22. Corea, G.; Fattorusso, E.; Lanzotti, V.; Taglialatela-Scafati, O.; Appendino, G.; Ballero, M.; Simon, P. N.; Dumontet, C.; Di Pietro, A. Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead J. Med. Chem. 2003, 46, 3395-3402
23. Corea, G.; Fattorusso, E.; Taglialatela-Scafati, O.; Appendino, G.; Ballero, M.; Sirnon, P. N. L.; Dumontet, C.; Di Pietro, A. Modified jatrophane diterpenes as modulators of multidrug resistance from Euphorbia dendroides L Bioorg. Med. Chem. 2003, 11, 5221-5227
24. Corea, G.; Fattorusso, E.; Lanzotti, V.; Motti, R.; Simon, P. N.; Dumontet, C.; Di Pietro, A. Jatrophane diterpenes as modulators of multidrug resistance. Advances of structure-activity relationships and discovery of the potent lead pepluanin A J. Med. Chem. 2004, 47, 988-992
25. Duarte, N.; Járdánházy, A.; Molnár, J.; Hilgeroth, A.; Ferreira, M. J. U. Synergistic interaction between P-glycoprotein modulators and epirubicine on resistant cancer cells Bioorg. Med. Chem. 2008, 16, 9323-9330
26. Duarte, N.; Varga, A.; Cherepnev, G.; Radics, R.; Molnar, J.; Ferreira, M. J. U. Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids Bioorg. Med. Chem. 2007, 15, 546-554
27. Appendino, G.; Della Porta, C.; Conseil, G.; Sterner, O.; Mercalli, E.; Dumontet, C.; Di Pietro, A. A new P-glycoprotein inhibitor from the caper spurge (Euphorbia lathyris) J. Nat. Prod. 2003, 66, 140-142
28. Reis, M.; Ferreira, R. J.; Santos, M. M. M.; dos Santos, D. J. V. A.; Molnár, J.; Ferreira, M. J. U. Enhancing macrocyclic diterpenes as multidrug-resistance reversers: structure-activity studies on jolkinol D derivatives J. Med. Chem. 2013, 56, 748-760
29. Jiao, W.; Dong, W. W.; Li, Z. F.; Deng, M. C.; Lu, R. H. Lathyrane diterpenes from Euphorbia lathyris as modulators of multidrug resistance and their crystal structures Bioorg. Med. Chem. 2009, 17, 4786-4792
30. Bicchi, C.; Appendino, G.; Cordero, C.; Rubiolo, P.; Ortelli, D.; Veuthey, J. L. HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction from Caper Spurge (Euphorbia lathyris) seed oil Phytochem. Anal. 2001, 12, 255-262
31. Tian, Y.; Xu, W.; Zhu, C.; Lin, S.; Li, Y.; Xiong, L.; Wang, S.; Wang, L.; Yang, Y.; Guo, Y.; Sun, H.; Wang, X.; Shi, J. Lathyrane diterpenoids from the roots of Euphorbia micractina and their biological activities J. Nat. Prod. 2011, 74, 1221-1229
32. Ferreira, A. M. V. D.; Carvalho, L. H. M.; Carvalho, M. J. M.; Sequeira, M. M.; Silva, A. M. S. Jatrophane and lathyrane diterpenoids from Euphorbia hyberna L Phytochemistry 2002, 61, 373-377
33. Appendino, G.; Tron, G. C.; Cravotto, G.; Palmisano, G.; Jakupovic, J. An expeditious procedure for the isolation of ingenol from the seeds of Euphorbia lathyris J. Nat. Prod. 1999, 62, 76-79
34. Hohmann, J.; Evanics, F.; Vasas, A.; Dombi, G.; Jerkovich, G.; Máthé, I. A novel lathyrane diterpenoid from the roots of Euphorbia lathyris J. Nat. Prod. 1999, 62, 176-178
35. Appendino, G.; Belloro, E.; Tron, G. C.; Jakupovic, J.; Ballero, M. Diterpenoids from Euphorbia pithyusa subsp. cupanii J. Nat. Prod. 1999, 62, 1399-1404
36. Taylor, M. D.; Smith, A. B., III; Furst, G. T.; Gunasekara, S. P.; Bevelle, C. A.; Cordell, G. A.; Farnsworth, N. R.; Kupchan, S. M.; Uchida, H. Plant anticancer agents. 28. New antileukemic jatrophone derivatives from Jatropha gossypiifolia: structural and stereochemical assignment through nuclear magnetic resonance spectroscopy J. Am. Chem. Soc. 1983, 105, 3177-3183
37. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. New colorimetric cytotoxicity assay for anticancer-drug screening J. Natl. Cancer Inst. 1990, 82, 1107-1112
38. Parthasarathi, R.; Subramanian, V.; Royb, D. R.; Chattaraj, P. K. Electrophilicity index as a possible descriptor of biological activity Bioorg. Med. Chem. 2004, 12, 5533-5543
39. Chattaraj, P. K.; Giri, S.; Soma, D. Update 2 of: electrophilicity index Chem. Rev. 2011, 111, PR43-PR75
40. Li, D.; Chen, L.; Li, Y.; Tian, S.; Sun, H.; Hou, T. ADMET evaluation in drug discovery. 13. Development of in silico prediction models for P-glycoprotein substrates Mol. Pharmaceutics 2014, 11, 716-726
41. Ferreira, R. J.; dos Santos, D. J. V. A.; Ferreira, M. J. U.; Guedes, R. C. Toward a better pharmacophore description of P-glycoprotein modulators, based on macrocyclic diterpenes from Euphorbia species J. Chem. Inf. Model. 2011, 51, 1315-1324
42. Gleeson, M. P. Generation of a set of simple, interpretable ADMET rules of thumb J. Med. Chem. 2008, 51, 817-834
43. Altschul, S. F.; Madden, T. L.; Schäffer, A. A.; Zhang, J.; Zhang, Z.; Miller, W.; Lipman, D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Nucleic Acids Res. 1997, 25, 3389-3402
44. Loo, T. W.; Bartlett, M. C.; Clarke, D. M. Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding J. Biol. Chem. 2003, 278, 13603-13606
45. Martin, C.; Berridge, G.; Mistry, P.; Higgins, C.; Charlton, P.; Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein Br. J. Pharmacol. 1999, 128 (2) 403-411
46. Batist, G.; Tulpule, A.; Sinha, B. K.; Katki, A. G.; Myers, C. E.; Cowan, K. H. Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells J. Biol. Chem. 1986, 261, 5544-5549
47. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision A.02; Gaussian Inc: Wallingford, CT, 2009.
48. Eswar, N.; Marti-Renom, M. A.; Webb, B.; Madhusudhan, M. S.; Eramian, D.; Shen, M.; Pieper, U.; Sali, A. Comparative protein structure modeling with MODELLER. Current Protocols in Bioinformatics; Wiley: New York, 2006; Suppl. 15, pp 5.6.1-5.6.30.
49. Laskoswki, R. A.; MacArthur, M. W.; Moss, D. S.; Thorton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures J. Appl. Crystallogr. 1993, 26, 283-291
50. Hooft, R. W.; Vriend, G.; Sander, C.; Abola, E. E. Errors in protein structures Nature 1996, 381, 272
51. Colovos, C.; Yeates, T. O. Verification of protein structures: patterns of nonbonded atomic interactions Protein Sci. 1993, 2, 1511-1519
52. 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. 2010, 31, 455-461
53. Humphrey, W.; Dalke, A.; Schulten, K. VMD: visual molecular dynamics J. Mol. Graphics 1996, 14 (1) 33
54. Lomize, M. A.; Lomize, A. L.; Pogozheva, I. D.; Mosberg, H. I. OPM: orientations of proteins in membranes database Bioinformatics 2006, 22, 623-625
55. Skjevik, Å. A.; Madej, B. D.; Walker, R. C.; Teigen, K. LIPID11: a modular framework for lipid simulations using Amber J. Phys. Chem. B 2012, 116, 11124-11136
56. Case, D. A.; Darden, T. A.; Cheatham, T. E.; Simmerling, C. L.; Wang, J.; Duke, R. E.; Luo, R.; Walker, R. C.; Zhang, W.; Merz, K. M.; Roberts, B.; Hayik, S.; Roitberg, A.; Seabra, G.; Swails, J.; Goetz, A. W.; Kolossváry, I.; Wong, K. F.; Paesani, F.; Vanicek, J.; Wolf, R. M.; Liu, J.; Wu, X.; Brozell, S. R.; Steinbrecher, T.; Gohlke, H.; Cai, Q.; Ye, X.; Wang, J.; Hsieh, M. J.; Cui, G.; Roe, D. R.; Mathews, D. H.; Seetin, M. G.; Salomon-Ferrer, R.; Sagui, C.; Babin, V.; Luchko, T.; Gusarov, S.; Kovalenko, A.; Kollman, P. A. AMBER 12; University of California: San Francisco, CA, 2012.
57. Hou, T.; Wang, J.; Li, Y.; Wang, W. Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking J. Comput. Chem. 2011, 32, 866-877
58. Genheden, S.; Kuhn, O.; Mikulskis, P.; Hoffmann, D.; Ryde, U. The normal-mode entropy in the MM/GBSA method: effect of system truncation, buffer region, and dielectric constant J. Chem. Inf. Model. 2012, 52, 2079-2088