Synthesis in vitro/in vivo evaluation and in silico physicochemical study of prodrug approach for brain targeting of alkylating agent

Medicinal Chemistry Research

Volumn 22, Issue 11, 2013, Pages 5324-5336

  Singh, Rajesh K ^a   Prasad, D N ^a   Bhardwaj, T R ^b  

^a Shivalik College of Pharmacy   (India)

^b ISF COLLEGE OF PHARMACY   (India)

Author keywords

Alkylating agent; Chemical delivery system; In silico ADME; In vitro in vivo studies; NBP assay

Indexed keywords

1 (4 NITROBENZYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] PYRIDINIUM BROMIDE; 1 (4 NITROBENZYL) 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] 1,4 DIHYDROPYRIDINE; 1 BENZYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] 1, 4 DIHYDROPYRIDINE; 1 BENZYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] PYRIDINIUM BROMIDE; 1 ETHYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] 1, 4 DIHYDROPYRIDINE; 1 ETHYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] PYRIDINIUM IODIDE; 1 PROPYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] 1, 4 DIHYDROPYRIDINE; 1 PROPYL 3 [(BIS(2 CHLOROETHYL)AMINO)CARBAMOYL] PYRIDINIUM BROMIDE; ALKYLATING AGENT; CHLORAMBUCIL; CHLORMETHINE; DICHLORODIETHYLAMINE; DIHYDROPYRIDINE DERIVATIVE; PRODRUG; SILVER NITRATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; COMPUTER MODEL; COMPUTER PROGRAM; CONTROLLED STUDY; DRUG DELIVERY SYSTEM; DRUG HALF LIFE; DRUG METABOLISM; DRUG SCREENING; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; OXIDATION; PHYSICAL CHEMISTRY; RAT;

EID: 84887431515     PISSN: 10542523     EISSN: 15548120     Source Type: Journal    
DOI: 10.1007/s00044-013-0537-0     Document Type: Article

References (34)

1. Al-Obaid AM, Farag HA, Khalil AA et al (2006) Synthesis and investigation of novel shelf-stable, brain-specific chemical delivery system. Saudi Pharm J 14(1):1-15
2. Balazs MK, Anderson A, Iwamoto RH, Lim P (1970) Synthesis of 4-{p-((2-chloroethyl)-(2-hydroxyethyl)amino)phenyl}butyric acid and its behaviours in the 4-(4-nitrobenzyl)pyridine assay procedure. J Pharm Sci 59(4):563-565
3. Bartzatt RL (2004) Synthesis and alkylating activity of a nitrogen mustard agent to penetrate the blood-brain barrier. Drug Deliv 11:19-26
4. Bodor N, Farag H (1983) Improved delivery through biological membrane. XI. A redox chemical drug-delivery system and its use for brain-specific delivery of phenylethylamine. J Med Chem 26:318-328
5. Bodor N, Farag HH, Brewster ME (1981) Site-specific sustained release of drugs to the brain. Science 214:1370-1372
6. Bodor N, Venkatraghavan V, Windwood D, Estes K, Brewster E (1989) Improved delivery through biological membranes. XLI. Brain-enhanced delivery of chlorambucil. Int J Pharm 53:195-208
7. Clark D (1999) Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood brain barrier penetration. J Pharm Sci 8(88):815-821
8. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumours diagnosed in the United States in 2005-2009. Neuro-Oncology 14(5):1-49
9. El-Sherbeny MA, Al-Salem HS, Sultan MA, Radwan MA, Farag HA, Ei-Subbagh HI (2003) Synthesis in vitro & in vivo evaluation of a delivery system for targeting anticancer drug to brain. Arch Pharm 336(10):445-455
10. Francisco AP, Perry MJ, Moreira R, Mendes E (2008). Alkylating agents, Chap 9. In: Misssailidis S (ed) Anticancer therapeutics. Wiley, Weinheim, p 133-158
11. Genka S, Deutsch J, Shetty UH, Stahle PL, John V, Lieberburg IM, Ali-Osman F, Rapoport SI, Greig NH (1993) Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil. Clin Exp Metastasis 11:131-140
12. Gomez-Bombrelli R, Gonzalez-Perez M, Calle E, Casado J (2012) Potential of the NBP method for the study of alkylation mechanism: NBP as a DNA-model. Chem Res Toxicol 25:1175-1191
13. Hirata T, Driscoll JS (1976) Potential CNS antitumor agents- phenothiazines I: nitrogen mustard derivatives. J Med Chem 65:1699-1701
14. Jorgensen WL (2009) Efficient drug lead discovery and optimization. Acc Chem Res 42(6):724-733
15. Kapuriya N, Kakadiya R, Dong H, Kumar A, Lee P-C, Zhang X, Chou T-C, Lee T-C, Chen C-H, Lam K, Marvania B, Shah e A, Su T-L (2011) Design, synthesis, and biological evaluation of novel water-soluble N-mustards as potential anticancer agents. Bioorg Med Chem 19:471-485
16. Kelder J, Grootenhuis P, Bayada D, Delbressine L, Ploemen J (1999) Polar molecular surface at a dominating determinant for oral absorption and brain penetration of drugs. Pharm Res 10(16):1514-1519
17. Li Z, CaulfieldT QiuY, Copland JA, Tun HW (2012) Pharmacokinetics of bendamustine in the central nervous system: chemoinformatic screening followed by validation in a murine model. Med Chem Commun 3:1526-1530
18. Lipinski C, Lombardo F, Dominy B, Feeney P (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 23:3-25
19. Mahmoud S, Mohammad A (2010) Brain-specific delivery of naproxen using different carrier systems. Arch Pharm Chem Life Sci 10:639-647
20. Molinspiration Cheminformatics, Bratislava, Slovak Republic. Available online http://www.molinspiration.com/services/properties.html. Accessed 22 April 2010
21. Mourelatos C, Kareli D, Dafa E, Argyraki M, Koutsourea A, Papakonstantinou I, Fousteris M, Pairas G, Nikolaropoulos S, Lialiaris TS (2012) Cytogenetic and antineoplastic effects by newly synthesised steroidal alkylators in lymphocytic leukaemia P388 cells in vivo. Mut Res 7:1-6
22. Palm K, Luthman K, Ungell A, Strandluno G, Artusson P (1996) Correlation of drug absorption with molecular surface properties. J Pharm Sci 1(85):32-39
23. Peng GW, Marquez VE, Driscoll JS (1975) Potential central nervous system antitumor agents. Hydantoin derivatives. J Med Chem 18(8):846-849
24. Phelan MJ, Bodor N (1989) Improved delivery through biological membranes. XXXVII. Synthesis and stability of novel redox derivatives of naproxen and indomethacin. Pharm Res 6(8):667-676
25. Pop E, Loftsson T, Bodor N (1991) Solubilization and stabilization of benzylpencillin chemical delivery system by 2-hydroxypropyl-β-cyclodextrin. Pharm Res 8:1044-1049
26. Prokai L, Prokai-Tatrai K, Bodor N (2000) Targeting drug to the brain by redox chemical drug delivery system. Med Res Rev 20:367-416
27. Raghavan KS, Shek E, Bodor N (1987) Improved delivery through biological membranes. XXX. Synthesis and biological aspects of a 1,4-dihydropyridine based chemical delivery system for brain-sustained delivery of hydroxy CCNU. Anticancer Drug Des 2(1):25-36
28. Scutaru AM, Wenzel M, Gust R (2011) Bivalent bendamustine and melphalan derivatives as anticancer agents. Eur J Med Chem 46:1604-1615
29. Sheha M, Al-Tayeb A, EI-Sherief H, Farag H (2003) New carrier for specific delivery to drugs to the brain. Bio Med Chem 11:1865-1872
30. Singh RK, Devi S, Prasad DN (2011) Synthesis, physicochemical and biological evaluation of CNS active 2-aminobenzophenone derivatives as potent skeletal muscle relaxant. Arab J Chem (in press) doi: 10.1016/j.arabjc.2011.11. 013
31. Singh RK, Prasad DN, Bhardwaj TR (2012a) Synthesis, alkylation activity and physicochemical evaluation of benzodiazpine-linked nitrogen mustard agent to penetrate the blood-brain barrier. Asian J Chem 24(12):5605-5608
32. Singh RK, Sharma S, Malik S, Sharma D, Prasad DN, Bhardwaj TR (2012b) Synthesis and study of chemical delivery system for targeting nitrogen mustard to the brain. Asian J Chem 24(12):5635-5638
33. Singh RK, Prasad DN, Bhardwaj TR (2012c) Synthesis, physicochemical properties and kinetic study of bis(2-chloroethyl)amine as cytotoxic agent for brain delivery. Arab J Chem (in press) doi: 10.1016/j.arabjc.2012.11.005
34. Stout DM, Meyers AI (1982) Recent advances in the chemistry of dihyropyridines. Chem Rev 82:223-243