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Review

Small endogenous molecules as moiety to improve targeting of CNS drugs

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Pages 93-107 | Received 18 May 2016, Accepted 27 Jun 2016, Published online: 15 Jul 2016

References

  • Lochhead JJ, Wolak DJ, Pizzo ME, et al. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. J Cereb Blood Flow Metab. 2015;35(3):371–381.
  • Dahan A, Zimmermann EM, Ben-Shabat S. Modern prodrug design for targeted oral drug delivery. Molecules. 2014;19:16489–16505.
  • Neuwelt A. Implications of the Blood-Brain Barrier and its manipulation. New York (NY): Plenum Medical Book Company; 2013.
  • Pardridge WM. Blood-brain barrier endogenous transporters as therapeutic targets: a new model for small molecule CNS drug discovery. Expert Opin Ther Targets. 2015;19:1059–1072.
  • Löscher W, Potschka H. Blood-Brain Barrier Active Efflux Transporters: ATP-Binding Cassette Gene Family. NeuroRx. 2005;2(1):86–98. doi:10.1602/neurorx.2.1.86
  • Mangas-Sanjuan V, Gonzalez-Alvarez M, Gonzalez-Alvarez I, et al. Drug penetration across the blood-brain barrier: an overview. Ther Deliv. 2010;1:535–562. .
  • Oller-Salvia B, Sánchez-Navarro M, Giralt E, et al. Blood–brain barrier shuttle peptides: an emerging paradigm for brain delivery. Chem Soc Rev. 2016. doi:10.1039/c6cs00076b.
  • Geiera EG, Schlessinger A, Fana H, et al. Structure-based ligand discovery for the large-neutral amino acid transporter 1, LAT-1. Pnas. 2013;110:5480–5485.
  • Vale N. Biomedical Chemistry: Current trends and developments. Section 3: Strategies to develop new and better drugs. Berlin: De Gruyter Open; 2015.
  • Hokari M, Wu HQ, Schwarcz R, et al. Facilitated brain uptake of 4-chlorokynureine and conversion to 7-chlorokynurenic acid. Neuropharmacol Neurotoxicol. 1996;8:15–18.
  • Salunkhe SS, Bhatia NM, Kawade VS, et al. Development of lipid based nanoparticulate drug delivery systems and drug carrier complexes for delivery to brain. J App Pharm Sci. 2015;5:110–129.
  • Bickel U, Yoshikawa T, Pardridge WM. Delivery of peptides and proteins through the blood-brain barrier. Adv Drug Deliv Rev. 2001;46:247279.
  • Vig BS, Huttunen KM, Laine K, et al. Amino acids as promoieties in prodrug design and development. Adv Drug Del Rev. 2013;65:1370–1385.
  • Salameh F, Karaman D, Mecca G, et al. Prodrugs targeting the central nervous system (CNS). World J Pharm Sci. 2015;4:208–237.
  • Gynther M, Laine K, Ropponen J, et al. Large neutral amino acid transporter enables brain drug delivery via prodrugs. J Med Chem. 2008;51:932–936.
  • Gynther M, Jalkanen A, Lehtonen M, et al. Brain uptake of ketoprofen-lysine prodrug in rats. Int J Pharm. 2010;399:121–128.
  • Giannola LI, Lamartina L, De Caro V. Synthesis and characterization of aminoacidic pro-drugs of valproic acid. Pharmazie. 1998;53:829–834.
  • De Caro V, Giandalia G, Siragusa MG, et al. N-Valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug. Med Chem. 2011;7:9–17.
  • De Caro V, Scaturro AL, Sutera FM, et al. N-Valproyl-L-Phenylalanine as new potential antiepileptic drug: synthesis, characterization and in vitro studies on stability, toxicity and anticonvulsant efficacy. Med Chem. 2015;11:30–40.
  • Sardo P, Rizzo V, Friscia S, et al. Inhibitory effects of N-valproyl-L-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity in rat brain slices. J Neural Transm. 2012;119:1249–1259.
  • Peura L, Malmioja K, Laine K, et al. Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: new prodrug design ideas for central nervous system delivery. Molecular Pharmaceutics. 2011;8:1857–1866.
  • Patel M, Mandava N, Gokulgandhi M, et al. Amino acid prodrugs: an approach to improve the absorption of HIV-1 protease inhibitor, lopinavir. Pharmaceuticals. 2014;7:433–452.
  • Agarwal S, Boddu SH, Jain R, et al. Peptide prodrugs: improved oral absorption of lopinavir, a HIV protease inhibitor. Int J Pharm. 2008;359:7–14.
  • Lupia RH, Ferencz N, Lertora JJ, et al. Comparative pharmacokinetics of two prodrugs of zidovudine in rabbits: enhanced levels of zidovudine in brain tissue. Antimicrob Agents Chemother. 1993;37:818–824.
  • Al-Ghananeem AM, Smith M, Coronel ML, et al. Advances in brain targeting and drug delivery of anti-HIV therapeutic agents. Expert Opin Drug Deliv. 2013;10:973–985.
  • Han HK, Oh DM, Amidon GL. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPT1 cells overexpressing a human peptide transporter. Pharm Res. 1998;15:1382–1386.
  • Moroni GN, Bogdanov PM, Briñón MC. Synthesis and in vitro antibacterial activity of novel 5ʹ-O-analog derivatives of zidovudine as potential prodrugs. Nucleosides Nucleotides Nucleic Acids. 2002;21:231–241.
  • Rouquayrol M, Gaucher B, Greiner J, et al. Synthesis and anti-HIV activity of glucose-containing prodrugs derived from saquinavir, indinavir and nelfinavir. Carbohydr Res. 2001;336:161–180.
  • Rouquayrol M, Gaucher B, Roche D, et al. Transepithelial transport of prodrugs of the HIV protease inhibitors saquinavir, indinavir, and nelfinavir across Caco-2 cell monolayers. Pharm Res. 2002;19:1704–1712.
  • Roche D, Greiner J, Aubertin AM, et al. Synthesis and in vitro biological evaluation of valine-containing prodrugs derived from clinically used HIV-protease inhibitors. Eur J Med Chem. 2008;43:1506–1518.
  • Zawilska JB, Wojcieszak J, Olejniczak AB. Prodrugs: A challenge for the drug development. Pharmacological Reports. 2013;65:1–14.
  • Pinnen F, Cacciatore I, Cornacchia C, et al. Synthesis and study of L-dopa-glutathione codrugs as new anti-Parkinson agents with free radical scavenging properties. J Med Chem. 2007;50:2506–2515.
  • Pinnen F, Cacciatore I, Cornacchia C, et al. CNS delivery of L-dopa by a new hybrid glutathione-methionine peptidomimetic prodrug. Amino Acids. 2012;42:261–269.
  • Sozio P, Cerasa LS, Abbadessa A, et al. Designing prodrugs for the treatment of Parkinson’s disease. Expert Opin Drug Discov. 2012;7:385–406.
  • Giannola LI, De Caro V, Giandalia G, et al. Synthesis and in vitro studies on a potential dopamine prodrug. Pharmazie. 2008;63:704–710.
  • Peura L, Malmioja K, Huttunen K, et al. Design, synthesis and brain uptake of LAT1-targeted amino acid prodrugs of dopamine. Pharm Res. 2013;30:2523–2537.
  • Estes KS, Brewster ME, Simpkins JW, et al. A novel redox system for CNS-directed delivery of estradiol causes sustained LH suppression in castrate rats. Life Sci. 1987;40:1327–1334.
  • Glasky AJ, Glasky MS, Ritzmann RF, et al. AIT-082, a novel purine derivative with neuroregenerative properties. Expert Opin Investig Drugs. 1997;6:1413–1417.
  • Taylor EM, Yan R, Hauptmann N, et al. AIT-082, a cognitive enhancer, is transported into brain by a nonsaturable influx mechanism and out of brain by a saturable efflux mechanism. J Pharmacol Exp Ther. 2000;293:813–821.
  • De Caro V, Sutera FM, Gentile C, et al. Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation. J Drug Target. 2015;23:910–925.
  • Sutera FM, De Caro V, Cannizzaro C, et al. Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence. Behav Brain Res. 2016 May 4. Forthcoming. doi:10.1016/j.bbr.2016.05.006
  • Singh VK, Subudhi BB. Development of reversible glutamine conjugate of methotrexate for enhanced brain delivery. Med Chem Res. 2014;24:624–635.
  • Singh VK, Subudhi BB. Development and characterization of lysine-methotrexate conjugate for enhanced brain delivery. Drug Deliv. 2014. doi:10.3109/10717544.2014.984369. [Epub ahead of print].
  • Decaux G, Gankam Kengne F, Couturier B, et al. Actual therapeutic indication of an old drug: urea for treatment of severely symptomatic and mild chronic hyponatremia related to SIADH. J Clin Med. 2014;3:1043–1049.
  • Dimmock JR, Vashishtha SC, Stables JP. Ureylene anticonvulsants and related compounds. Pharmazie. 2000;55:490–494.
  • Kashaw SK, Kashaw V, Mishra P, et al. Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea. Eur J Med Chem. 2009;44:4335–4343.
  • He X, Zhong M, Yang J, et al. Synthesis and anticonvulsant activity of 1-(2-(8-(benzyloxy)quinolin-2-yl)-1-butyrylcyclopropyl)-3-substituted urea derivatives. Chem Biol Drug Des. 2012;79:771–779.
  • Kaymakçioğlu BK, Rollas S, Körceğez E, et al. Synthesis and biological evaluation of new N-substituted-N’-(3,5-di/1,3,5-trimethylpyrazole-4-yl)thiourea/urea derivatives. Eur J Pharm Sci. 2005;26:97–103.
  • Chayah M, Camacho ME, Carrión MD, et al. N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase. ChemMedComm. 2016;7:667–678.
  • Shimshoni JA, Bialer M, Wlodarczyk B, et al. Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid. J Med Chem. 2007;50:6419–6427.
  • Shimshoni JA, Yagen B, Pessah N, et al. Anticonvulsant profile and teratogenicity of 3,3-dimethylbutanoylurea: A potential for a second generation drug to valproic acid. Epilepsia. 2008;49:1202–1212.
  • Shimshoni JA, Yagen B, Wlodarczyk B, et al. Evaluation of stereoselective anticonvulsant, teratogenic, and pharmacokinetic profile of valnoctylurea (capuride): A chiral stereoisomer of valproic acid urea derivative. Epilepsia;. 2010;51:323–332.
  • Kaufmann D, Bialer M, Shimshoni JA, et al. Synthesis and evaluation of antiallodynic and anticonvulsant activity of novel amide and urea derivatives of valproic acid analogues. J Med Chem;. 2009;52:7236–7248.
  • Ravikumar V, Sen DJ. Structure activity relationship studies of synthesized urea diamides on CNS depression and sleeping time potentiation effect. Int J Drug Dev Res. 2010;2:512–528.
  • Szacoń E, Rządkowska M, Kaczor AA, et al. Synthesis, central nervous system activity and structure-activity relationships of novel 1-(1-alkyl-4-aryl-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives. Molecules. 2015;20:3821–3840.
  • Arce MP, Rodríguez-Franco MI, González-Muñoz GC, et al. Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzheimer’s disease. J Med Chem. 2009;52:7249–7257.
  • Martínez A, Lanot C, Perez C, et al. Lipase-catalysed synthesis of new acetylcholinesterase inhibitors: N-benzylpiperidine aminoacid derivatives. Bioorg Med Chem. 2000;8:731–738.
  • Muñoz-Ruiz P, Rubio L, García-Palomero E, et al. Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer’s disease. J Med Chem. 2005;48:7223–7233.
  • Bloom GS. Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014;71:505–508.
  • Lopez-Ibarra D, Munoz-Torrero Cantin NM, Inestrosa GEV, et al. Beta-amyloid-directed multitarget compounds for the treatment of Alzheimer’s. Patent WO 2013167711 A1. 2013.
  • Tamborini L, Conti P, Pinto A, et al. Synthesis of new b- and g-benzyloxy-S glutamic acid derivatives and evaluation of their activity as inhibitors of excitatory amino acid transporters. Tetrahedron. 2009;65:6083–6089.
  • Carelli V, Liberatore F, Scipione L, et al. Synthesis and biological evaluation of GABA derivatives able to cross the blood-brain barrier in rats. Bioorg Med Chem Lett. 2003;13:3765–3769.
  • Whitworth TL, Quick MW. Upregulation of gamma-aminobutyric acid transporter expression: role of alkylated gamma-aminobutyric acid derivatives. Biochem Soc Trans. 2001;29:736–741.
  • Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6:108–113.
  • Yogeeswari P, Ragavendran JV, Sriram D, et al. Newer N-phthaloyl GABA derivatives with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain. Pharmacology. 2008;81:21–31.
  • Yogeeswari P, Ragavendran JV, Sriram D. GABA analogs for CNS drug discovery. Recent Pat CNS Drug Discov. 2006;1:113–118.
  • Yogeeswari P, Sriram D, Thirumurugan R, et al. Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design. J Med Chem. 2005;48:6202–6211.
  • Usifoh CO, Lambert DM, Wouters J, et al. Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids. Arch Pharm (Weinheim). 2001;334:323–331.
  • Mendyk A, Salat K, Librowski T, et al. Influence of new g-aminobutyric acid amide derivatives and its phthalimide precursors on the central nervous system activity in mice. Pol J Pharmacol. 2001;53:689–693.
  • Ragavendran JV, Sriram D, Patel SK, et al. Design and synthesis of anticonvulsants from a combined phthalimide-GABA-anilide and hydrazine pharmacophore. Eur J Med Chem. 2007;42:146–151.
  • Ragavendran JV, Sriram D, Kotapati S, et al. Newer GABA derivatives for the treatment of epilepsy including febrile seizures: a bioisosteric approach. Eur J Med Chem. 2008;43:2650–2655.
  • Chung MC, Malatesta P, Bosquesi PL, et al. Advances in drug design based on the amino acid approach: taurine analogues for the treatment of CNS diseases. Pharmaceuticals (Basel). 2012;5:1128–1146.
  • Anderson WR, Simpkins JW, Woodard PA, et al. Anxiolytic activity of a brain delivery system for GABA. Psychopharmacology. 1987;92:157–163.
  • Creasey NH, Green ALJ. 2-Hydroxyiminomethyl-N-methylpyridinium methanesulphonate (P2S), an antidote to organophosphorus poisoning. Its preparation, estimation and stability. Pharm Pharmacol. 1959;11:485–490.
  • Brewster ME, Raghavan K, Pop E, et al. Enhanced delivery of ganciclovir to the brain through the use of redox targeting. Antimicrob Agents Chemother. 1994;38:817–823.
  • Wu WM, Pop E, Shek E, et al. Brain-specific chemical delivery systems for beta-lactam antibiotics. In vitro and in vivo studies of some dihydropyridine and dihydroiso-quinoline derivatives of benzylpenicillin in rats. J Med Chem. 1989;32:1782–1788.
  • Wu WM, Pop E, Shek E, et al. Brain and CSF specific chemical delivery systems for beta-lactam antibiotics. Study of two dihydropyridine derivatives of benzyl-penicillin in rabbits and dogs. Drug Des Deliv. 1990;7:33–43.
  • Anderson WR, Simpkins JW, Brewster ME, et al. Evidence for suppression of serum LH without elevation in serum estradiol or prolactin with a brain-enhanced redox delivery system for estradiol. Life Sci. 1988;42:1493–1502.
  • Prokai-Tatrai K, Szarka S, Nguyen V, et al. “All in the mind”? Brain-targeting chemical delivery system of 17β-estradiol (Estredox) produces significant uterotrophic side effect. Pharm Anal Acta. 2012;(Sup 7): doi:10.4172/2153-2435.S7-002
  • Bodor NS. Methods for the treatment of male and female sexual dysfunction. Patent WO 2005011618 A2. 2005.
  • Halmos T, Santarromana M, Antonakis K, et al. Synthesis of glucose-chlorambucil derivatives and their recognition by the human GLUT1 glucose transporter. Eur J Pharmacol. 1996;318:477–484.
  • Uriel C, Egron MJ, Santarromana M, et al. Hexose keto-C-glycoside conjugates: design, synthesis, Cytotoxicity, and evaluation of their affinity for the Glucose Transporter Glut-1. Bioorg Med Chem. 1996;4:2081–2090.
  • Fernández C, Nieto O, Rivas E, et al. Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents. Carbohydr Res. 2000;327:353–365.
  • Bonina F, Puglia C, Rimoli MG, et al. Glycosyl derivatives of Dopamine and L-Dopa as antiparkinson prodrugs: synthesis, pharmacological activity and in vitro stability studies. J Drug Targeting. 2003;11:25–36.
  • Bonina FP, Arenare L, Ippolito R, et al. Synthesis, pharmacokinetics and anticonvulsant activity of 7-chlorokynurenic acid prodrugs. Int J Pharm. 2000;202:79–88.
  • Battaglia G, La Russa M, Bruno V, et al. Systemically administered D-glucose conjugates of 7-chlorokynurenic acid are centrally available and exert anticonvulsant activity in rodents. Brain Res. 2000;869:149–156.
  • Bonina F, Puglia C, Rimoli MG, et al. Synthesis and in vitro chemical and enzymatic stability of glycosyl 3ʹ-azido-3ʹ-deoxythymidine derivatives as potential anti-HIV agents. Eur J Pharm Sci. 2002;16:167–174.
  • Chen Q, Gong T, Liu J, et al. Synthesis, in vitro and in vivo characterization of glycosyl derivatives of ibuprofen as novel prodrugs for brain drug delivery. J Drug Target. 2009;17:318–328.
  • Habibuddin M, Pal M, Pal SP. Neuropharmacology of amide derivatives of P-GABA. Indian J Exp Biol. 1992;30:578–582.
  • Geerts H. AIT-082 NeoTherapeutics Inc. IDrugs. 1998;1:694–699.
  • Grundman M, Farlow M, Peavy G, et al. A phase I study of AIT-082 in healthy elderly volunteers. J Mol Neurosci. 2002;18:283–293.
  • Chemicalize.org by ChemAxon Ltd; 2016. [cited 2016 May 14]. Available from: http://www.chemaxon.com.
  • Smith QR. Transport of glutamate and other amino acids at the blood-brain barrier. J Nutr. 2000;130:1016S–22S.
  • Homma M, Suzuki H, Kusuhara H, et al. High-affinity efflux transport system for glutathione conjugates on the luminal membrane of a mouse brain capillary endothelial cell line (MBEC4). J Pharmacol Exp Ther. 1999;288:198–203.
  • Vaz SH, Jørgensen TN, Cristóvão-Ferreira S, et al. Sebastião AM Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes. J Biol Chem. 2011;286:40464–40476.
  • Dagenais C, Rousselle C, Pollack GM, et al. Development of an in situ mouse brain perfusion model and its application to mdr 1 a P-Glycoprotein-deficient mice. J Cereb Blood Flow Metab. 2000;20:381–386.
  • Tan IL, McArthur JC. HIV-associated neurological disorders: a guide to pharmacotherapy. CNS Drugs. 2012;26:123–134.
  • Gannon P, Khan MZ, Kolson DL. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol. 2011;24:275–283.
  • Asano T, Spector S. Identification of inosine and hypoxanthine as endogenous ligands for the brain benzodiazepine-binding sites. Proc Natl Acad Sci USA. 1979;76:977–981.
  • Stanimirovic DB, Bani-Yaghoub M, Perkins M, et al. Blood-brain barrier models: in vitro to in vivo translation in preclinical development of CNS-targeting biotherapeutics. Expert Opin Drug Discov. 2015;10:141–155.

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