Enhancing the anti-lymphoma potential of 3, 4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: Mechanisms and pathways to cell death

Investigational New Drugs

Volumn 30, Issue 4, 2012, Pages 1471-1483

  Wasik, Agata M ^a   Gandy, Michael N ^b   McIldowie, Matthew ^b   Holder, Michelle J ^a   Chamba, Anita ^a   Challa, Anita ^a   Lewis, Katie D ^b   Young, Stephen P ^a   Scheel Toellner, Dagmar ^a   Dyer, Martin J ^c   Barnes, Nicholas M ^d   Piggott, Matthew J ^b   Gordon, John ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c MRC TOXICOLOGY UNIT   (United Kingdom)

^d UNIVERSITY DEPARTMENT OF MEDICINE   (United Kingdom)

Author keywords

Apoptosis; Bcl 2; Cytotoxicity; Lymphoma; MDMA

Indexed keywords

3,4 METHYLENEDIOXYMETHAMPHETAMINE; 3,4 METHYLENEDIOXYMETHAMPHETAMINE DERIVATIVE; ANTINEOPLASTIC AGENT; CARRIER PROTEIN; MONOAMINE TRANSPORTER; PHENYL GROUP; PROTEIN BCL 2; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BCL2 GENE; BURKITT LYMPHOMA; CELL DEATH; CHEMICAL MODIFICATION; CHEMOSENSITIVITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; GENE EXPRESSION; LIPOPHILICITY; LYMPHOMA CELL; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN EXPRESSION; TRANSGENE;

B-LYMPHOCYTES; BURKITT LYMPHOMA; CELL DEATH; CELL LINE, TUMOR; DRUG DESIGN; HUMANS; N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; PROTO-ONCOGENE PROTEINS C-BCL-2; SIGNAL TRANSDUCTION;

EID: 84866743613     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-011-9730-5     Document Type: Article

References (43)

1. Serafeim A, Grafton G, Chamba A, Gregory CD, Blakely RD, Bowery NG, Barnes NM, Gordon J. (2002) 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors. Blood 99:2545-2553
2. Meredith EJ, Chamba A, Holder MJ, Barnes NM, Gordon J. (2005) Close encounters of the monoamine kind: immune cells betray their nervous disposition. Immunology 115:289-295
3. Serafeim A, Holder MJ, Grafton G, Chamba A, Drayson MT, Luong QT, Bunce CM, Gregory CD, Barnes NM, Gordon J. (2003) Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells. Blood 101:3212-3219
4. Meredith EJ, Holder MJ, Chamba A, Challa A, Drake-Lee A, Bunce CM, Drayson MT, Pilkington G, Blakely RD, Dyer MJ, Barnes NM, Gordon J. (2005) The serotonin transporter. (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential anti-tumor target for psychotropics. FASEB J 19:1187-1189
5. Chamba A, Holder MJ, Jarrett RF, Shield L, Toellner KM, Drayson MT, Barnes NM, Gordon J. SLC6A4 expression and anti-proliferative responses to serotonin transporter ligands chlomipramine and fluoxetine in primary B-cell malignancies. Leuk Res 34:1103-1106
6. Braun U, Shulgin AT, Braun G. (1980) Centrally active N-substituted analogs of 3, 4-methylenedioxyphenylisopropylamine. (3, 4- methylenedioxyamphetamine). J Pharm Sci 69:192-195
7. Braun U, Shulgin AT, Braun G. (1980) Research on the central activity and analgesia of N-substituted analogs of the amphetamine derivative 3, 4-methylenedioxyphenylisopropylamine. Arzneimittelforschung 30:825-830
8. Nichols DE, Hoffman AJ, Oberlender RA, Jacob P 3rd, Shulgin AT. (1986) Derivatives of 1-(1, 3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class. J Med Chem 29:2009-2015
9. Shulgin A, Shulgin A. (1991) Phenethylamines I have known and loved: A chemical love story transform Pr Berkeley, California
10. Nash JF, Nichols DE. (1991) Microdialysis studies on 3, 4- methylenedioxyamphetamine and structurally related analogues. Eur J Pharmacol 200:53-58
11. Gandy MN, McIldowie M, Lewis K, Wasik AM, Salomonczyk D, Wagg K, Millar ZA, Tindiglia D, Huot P, Johnston T, Thiele S, Nguyen B, Barnes NM, Brotchie JM, Martin-Inverson MT, Nash J, Gordon J, Piggott MJ. (2010) Redesigning the designer drug ecstasy: non-psychoactive MDMA analogues exhibiting Burkitt's lymphoma cytotoxicity. Med Chem Comm 1:287-293
12. Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY, Prokopenko VV. (2005) Virtual computational chemistry laboratory-design and description. J Comput Aided Mol Des 19:453-463
13. Steward LJ, Ge J, Bentley KR, Barber PC, Hope AG, Lambert JJ, Peters JA, Blackburn TP, Barnes NM. (1995) Evidence that the atypical 5-HT3 receptor ligand, [3H]-BRL46470, labels additional 5-HT3 binding sites compared to [3H]-granisetron. Br J Pharmacol 116:1781-1788
14. Bohm HJ, Banner D, Bendels S, Kansy M, Kuhn B, Muller K, Obst-Sander U, Stahl M. (2004) Fluorine in medicinal chemistry. Chembiochem 5:637-643
15. Smart BE. (2001) Fluorine substutuent effects. (on bioactivity). J Fluorine Chem 109:3-11
16. Cornish-Bowden A, Koshland DE Jr. (1975) Diagnostic uses of the Hill. (Logit and Nernst) plots. J Mol Biol 95:201-212
17. Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S, Smulson M. (1999) Role of poly(ADP-ribose) polymerase. (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 274:22932-22940
18. Cadet JL, Krasnova IN, Jayanthi S, Lyles J. (2007) Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 11:183-202
19. Beckman JW, Wang Q, Guengerich FP. (2008) Kinetic analysis of correct nucleotide insertion by a Y-family DNA polymerase reveals conformational changes both prior to and following phosphodiester bond formation as detected by tryptophan fluorescence. J Biol Chem 283:36711-36723
20. Blatt NB, Boitano AE, Lyssiotis CA, Opipari AW Jr, Glick GD. (2009) Bz-423 superoxide signals B cell apoptosis via Mcl-1, Bak, and Bax. Biochem Pharmacol 78:966-973
21. Tetko IV, Tanchuk VY. (2002) Application of associative neural networks for prediction of lipophilicity in ALOGPS 2.1 program. J Chem Inf Comput Sci 42:1136-1145
22. Tetko IV, Bruneau P. (2004) Application of ALOGPS to predict 1- octanol/water distribution coefficients, logP, and logD, of Astra- Zeneca in-house database. J Pharm Sci 93:3103-3110
23. Yamamoto B, Zhu W. (1998) The effects of methamphetamine on the production of free radicals and oxidative stress. J Pharmacol Exp Ther 287:107-114
24. Davidson C, Gow A, Lee T, Ellinwood E. (2001) Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev 36(1):1-22
25. Yamamoto BK, Bankson MG. (2005) Amphetamine neurotoxicity: cause and consequence of oxidative stress. Crit Rev Neurobiol 17:87-117
26. Montiel-Duarte C, Ansorena E, Lopez-Zabalza M, Cenarruzabeitia E, IraburuM(2004) Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3, 4-methylenedioxymethamphetamine. ("ecstasy") on hepatic stellate cells. Biochem Pharmacol 67:1025-1033
27. Monks TJ, Jones DC, Bai F, Lau SS. (2004) The role of metabolism in 3, 4-(+)-methylenedioxyamphetamine and 3, 4-(+)- methylenedioxymethamphetamine. (ecstasy) toxicity. Ther Drug Monit 26:132-136
28. Milhazes N, Cunha-Oliveira T, Martins P, Garrido J, Oliveira C, Rego AC, Borges F. (2006) Synthesis and cytotoxic profile of 3, 4- methylenedioxymethamphetamine. ("ecstasy") and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship. Chem Res Toxicol 19:1294-1304
29. Keizers PH, de Graaf C, de Kanter FJ, Oostenbrink C, Feenstra KA, Commandeur JN, Vermeulen NP. (2005) Metabolic regio- and stereoselectivity of cytochrome P450 2D6 towards 3, 4-methylenedioxy-Nalkylamphetamines: in silico predictions and experimental validation. J Med Chem 48:6117-6127
30. Capela JP, Carmo H, Remiao F, Bastos ML, Meisel A, Carvalho F. (2009) Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39:210-271
31. Callahan BT, Cord BJ, Yuan J, McCann UD, Ricaurte GA. (2001) Inhibitors of Na(+)/H(+) and Na(+)/Ca(2+) exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity. J Neurochem 77:1348-1362
32. Verrico CD, Miller GM, Madras BK. (2007) MDMA. (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology. (Berl) 189:489-503
33. Simantov R, Tauber M. (1997) The abused drug MDMA. (Ecstasy) induces programmed death of human serotonergic cells. FASEB J 11(2):141-146
34. Montgomery T, Buon C, Eibauer S, Guiry PJ, Keenan AK, McBean GJ. (2007) Comparative potencies of 3, 4-methylenedioxymethamphetamine. (MDMA)' analogues as inhibitors of [3H] noradrenaline and [3H]5-HT transport in mammalian cell lines. Br J Pharmacol 152:1121-1130
35. Hayat S, Williams RJ, Rattray M. (2006) Serotonin transporter expression is not sufficient to confer cytotoxicity to 3, 4-methylenedioxymethamphetamine. (MDMA)' in vitro. J Psychopharmacol 20:257-263
36. Meredith EJ, Holder MJ, Rosen A, Lee AD, Dyer MJ, Barnes NM, Gordon J. (2006) Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin's lymphoma. Proc Natl Acad Sci USA 103. (36):13485-13490
37. Biasutto L, Dong LF, Zoratti M, Neuzil J. Mitochondrially targeted anti-cancer agents. Mitochondrion 10:670-681
38. Christman JE, Miller DS, Coward P, Smith LH, Teng NN. (1990) Study of the selective cytotoxic properties of cationic, lipophilic mitochondrial-specific compounds in gynecologic malignancies. Gynecol Oncol 39:72-79
39. Huszar M, Varga A, Horvath A, Lorand T, Agocs A, Idei M, Mandl J, Vantus T, Keri G. Comparative characterization of experimental and calculated lipophilicity and anti-tumour activity of isochromanone derivatives. Curr Med Chem 17:321-333
40. Adams DJ, da Silva MW, Flowers JL, Kohlhagen G, Pommier Y, Colvin OM, Manikumar G, Wani MC. (2006) Camptothecin analogs with enhanced activity against human breast cancer cells. I. Correlation of potency with lipophilicity and persistence in the cleavage complex. Cancer Chemother Pharmacol 57:135-144
41. Maliepaard M, de Mol NJ, Janssen LH, van der Neut W, Verboom W, Reinhoudt DN. (1992) Role of lipophilicity in the in vitro antitumour activity of a series of new mitosene compounds. Anticancer Drug Des 7(5):415-425
42. Soderberg L, Haag L, Hoglund P, Roth B, Stenberg P, Wahlgren M. (2009) The effects of lipophilic substances on the shape of erythrocytes demonstrated by a new in vitro-method. Eur J Pharm Sci 36(4-5):458-464
43. Sanderson KL, Butler L, Ingram VM. (1997) Aggregates of a betaamyloid peptide are required to induce calcium currents in neuron-like human teratocarcinoma cells: relation to Alzheimer's disease. Brain Res 744(1):7-14