Determination of Small Molecule ABAD Inhibitors Crossing Blood-Brain Barrier and Pharmacokinetics

Journal of Alzheimer's Disease

Volumn 42, Issue 1, 2014, Pages 333-344

  Vangavaragu, Jhansi Rani ^a   Valasani, Koteswara Rao ^a   Fang, Du ^a   Williams, Todd D ^b   Yan, Shirley Shidu ^a  

^a UNIVERSITY OF KANSAS   (United States)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

ABAD inhibitors; amyloid ; benzothiazole phosphonates; blood brain barrier; pharmacokinetics

Indexed keywords

ACETONITRILE; AMYLOID BETA BINDING ALCOHOL DEHYDROGENASE INHIBITOR; METHANOL; OXIDOREDUCTASE INHIBITOR; UNCLASSIFIED DRUG; 3 HYDROXYACYL COENZYME A DEHYDROGENASE; ENZYME INHIBITOR;

ACCURACY; AREA UNDER THE CURVE; ARTICLE; BLOOD BRAIN BARRIER; BLOOD SAMPLING; BRAIN; CEREBROSPINAL FLUID; DRUG DETERMINATION; DRUG HALF LIFE; DRUG STABILITY; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIMIT OF DETECTION; LIMIT OF QUANTITATION; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; TANDEM MASS SPECTROMETRY; TEMPERATURE; TIME TO MAXIMUM PLASMA CONCENTRATION; ALZHEIMER DISEASE; ANIMAL; ANTAGONISTS AND INHIBITORS; CALIBRATION; ELECTROSPRAY MASS SPECTROMETRY; METABOLISM; VALIDATION STUDY;

3-HYDROXYACYL COA DEHYDROGENASES; ALZHEIMER DISEASE; ANIMALS; BLOOD-BRAIN BARRIER; BRAIN; CALIBRATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ENZYME INHIBITORS; MICE; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TANDEM MASS SPECTROMETRY;

EID: 84930667267     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-140252     Document Type: Article

References (43)

1. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107, 18670-18675.
2. Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD (2009) Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 106, 14670-14675.
3. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD (2005) Mitochondrial Abeta: A potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J 19, 2040-2041.
4. Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med 14, 45-53.
5. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: Superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21, 4923-4930.
6. Lunnon K, Ibrahim Z, Proitsi P, Lourdusamy A, Newhouse S, Sattlecker M, Furney S, Saleem M, Soininen H, Kloszewska I, Mecocci P, Tsolaki M, Vellas B, Coppola G, Geschwind D, Simmons A, Lovestone S, Dobson R, Hodges A, AddNeuroMed C (2012) Mitochondrial dysfunction and immune activation are detectable in early Alzheimer's disease blood. J Alzheimers Dis 30, 685-710.
7. Yan SD, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D (1997) An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature 389, 689-695.
8. Manczak M, Calkins MJ, Reddy PH (2011) Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: Implications for neuronal damage. Hum Mol Genet 20, 2495-2509.
9. Du H, Guo L, Zhang W, Rydzewska M, Yan S (2011) Cyclophilin D deficiency improves mitochondrial function and learning/memory in aging Alzheimer disease mouse model. Neurobiol Aging 32, 398-406.
10. Mao P, Manczak M, Calkins MJ, Truong Q, Reddy TP, Reddy AP, Shirendeb U, Lo HH, Rabinovitch PS, Reddy PH (2012) Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer's disease: Implications for neuroprotection and lifespan extension. Hum Mol Genet 21, 2973-2990.
11. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A 105, 19318-19323.
12. Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, Nagai T, Mizoguchi H, Ibi D, Hori O, Ogawa S, Stern DM, Yamada K, Yan SS (2009)RAGE-mediated signaling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. Proc Natl Acad Sci U S A 106, 20021-20026.
13. Eckert A, Hauptmann S, Scherping I, Rhein V, Muller-Spahn F, Gotz J, Muller WE (2008) Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice. Neurodegener Dis 5, 157-159.
14. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15, 1437-1449.
15. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 304, 448-452.
16. Valasani KR, Chaney MO, Day VW, Shidu Yan S (2013) Acetylcholinesterase inhibitors: Structure based design, synthesis, pharmacophore modeling, and virtual screening. J Chem Inf Model 53, 2033-2046.
17. Yang SY, He XY, Schulz H (2005) Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol Metab 16, 167-175.
18. He XY, Merz G, Yang YZ, Pullakart R, Mehta P, Schulz H, Yang SY (2000) Function of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism. Biochim Biophys Acta 1484, 267-277.
19. He XY, Merz G, Mehta P, Schulz H, Yang SY (1999) Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17beta-hydroxysteroid dehydrogenase. J Biol Chem 274, 15014-15019.
20. He XY, Schulz H, Yang SY (1998) A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease. J Biol Chem 273, 10741-10746.
21. Ofman R, Ruiter JP, Feenstra M, Duran M, Poll-The BT, Zschocke J, Ensenauer R, Lehnert W, Sass JO, Sperl W, Wanders RJ (2003) 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene. Am J Hum Genet 72, 1300-1307.
22. He XY, Yang YZ, Peehl DM, Lauderdale A, Schulz H, Yang SY (2003) Oxidative 3alpha-hydroxysteroid dehydrogenase activity of human type 10 17beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 87, 191-198.
23. Ivell R, Balvers M, Anand RJ, Paust HJ, McKinnell C, Sharpe R (2003) Differentiation-dependent expression of 17betahydroxysteroid dehydrogenase, type 10, in the rodent testis: Effect of aging in Leydig cells. Endocrinology 144, 3130-3137.
24. He XY, Wegiel J, Yang YZ, Pullarkat R, Schulz H, Yang SY (2005) Type 10 17beta-hydroxysteroid dehydrogenase catalyzing the oxidation of steroid modulators of gammaaminobutyric acid typeAreceptors. Mol Cell Endocrinol 229, 111-117.
25. Takuma K, Yao J, Huang J, Xu H, Chen X, Luddy J, TrillatA C, Stern DM, Arancio O, Yan SS (2005)ABADenhances Abetainduced cell stress via mitochondrial dysfunction. FASEB J 19, 597-598.
26. Yan Y, Liu Y, Sorci M, Belfort G, Lustbader JW, Yan SS, Wang C (2007) Surface plasmon resonance and nuclear magnetic resonance studies of ABAD-Abeta interaction. Biochemistry 46, 1724-1731.
27. Rao VK, Carlson EA, Yan SS (2013) Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochim Biophys Acta. doi: 10.1016/j.bbadis. 2013.09.003
28. Yan SD, Stern DM (2005) Mitochondrial dysfunction and Alzheimer's disease: Role of amyloid-beta peptide alcohol dehydrogenase (ABAD). Int J Exp Pathol 86, 161-171.
29. Valasani KR, Vangavaragu JR, Day VW, Yan SS (2014) Structure based design, synthesis, pharmacophore modeling, virtual screening, and molecular docking studies for identification of novel cyclophilin D inhibitors. J Chem Inf Model 54, 902-912.
30. Yan SD, Shi Y, Zhu A, Fu J, Zhu H, Zhu Y, Gibson L, Stern E, Collison K, Al-Mohanna F, Ogawa S, Roher A, Clarke SG, Stern DM (1999) Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity. J Biol Chem 274, 2145-2156.
31. Xie Y, Deng S, Chen Z, Yan S, Landry DW (2006) Identification of small-molecule inhibitors of the Abeta-ABAD interaction. Bioorg Med Chem Lett 16, 4657-4660.
32. Somogyi G, Nishitani S, Nomi D, Buchwald P, Prokai L, Bodor N (1998) Targeted drug delivery to the brain via phosphonate derivatives - I. Design, synthesis and evaluation of an anionic chemical delivery system for testosterone. Int J Pharm 166, 15-26.
33. Somogyi G, Buchwald P, Nomi D, Prokai L, Bodor N (1998) Targeted drug delivery to the brain via phosphonate derivatives - II. Anionic chemical delivery system for zidovudine (AZT). Int J Pharm 166, 27-35.
34. Somogyi G, Buchwald P, BodorN(2002) Targeted drug delivery to the central nervous system via phosphonate derivatives (Anionic delivery system for testosterone). Pharmazie 57, 135-137.
35. Rao VK, Reddy SS, Krishna BS, Reddy CS, Reddy NP, Reddy TC M, Raju CN, Ghosh SK (2011) Design, synthesis and anti colon cancer activity evaluation of phosphorylated derivatives of lamivudine (3TC). Lett Drug Des Discov 8, 59-64.
36. Rao VK, Rao AJ, Reddy SS, Raju CN, Rao PV, Ghosh SK (2010) Synthesis, spectral characterization and biological evaluation of phosphorylated derivatives of galanthamine. Eur J Med Chem 45, 203-209.
37. Valasani KR, Hu G, Chaney MO, Yan SS (2013) Structurebased design and synthesis of benzothiazole phosphonate analogues with inhibitors of human ABAD-Abeta for treatment of Alzheimer's disease. Chem Biol Drug Des 81, 238-249.
38. Valaasani KR, Sun Q, Hu G, Li J, Du F, Guo Y, Carlson EA, Gan X, Yan SS (2014) Identification of human ABAD inhibitors for rescuing Abeta-mediated mitochondrial dysfunction. Curr Alzheimer Res 11, 128-136.
39. (2001) Guidance for Industry-Bioanalytical Method Validation. US Food and Drug Administration.
40. Lv J, Pan L, Ye Y, ZhouY(2007)Asensitive and selective RPHPLC method for simultaneous determination of picroside-I and picroside-II in rat plasma and its application in pharmacokinetics studies. J Sep Sci 30, 2466-2472.
41. Samanidou VF, Nika MK, Papadoyannis IN (2007) Development of an HPLC method for the monitoring of tricyclic antidepressants in biofluids. J Sep Sci 30, 2391-2400.
42. Cheng S, Qiu F, Wang S, He J (2007) HPLC analysis and pharmacokinetics of icariin in rats. J Sep Sci 30, 1307-1312.
43. Xue YJ, Yan JH, Arnold M, Grasela D, Unger S (2007) Quantitative determination of BMS-378806 in human plasma and urine by high-performance liquid chromatography/tandem mass spectrometry. J Sep Sci 30, 1267-1275.