Physicochemical and drug metabolism characterization of a series of 4-aminoquinoline-3-hydroxypyridin-4-one hybrid molecules with antimalarial activity

Expert Opinion on Drug Metabolism and Toxicology

Volumn 10, Issue 10, 2014, Pages 1313-1324

  Thelingwani, Roslyn ^a,b   Bonn, Britta ^c   Chibale, Kelly ^b   Masimirembwa, Collen ^a,b  

^a African Institute of Biomedical Science and Technology   (Zimbabwe)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

Biotransformation; CYP inhibition; Hybrid analogs; Metabolic clearance

Indexed keywords

3 HYDROXY 4 PYRIDONE DERIVATIVE; 4 AMINOQUINOLINE 3,4 HYDROXYPYRIDINONE HYBRID; ANTIMALARIAL AGENT; CHLOROQUINE; CLOZAPINE; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; MIDAZOLAM; PROPRANOLOL; UNCLASSIFIED DRUG; AMINOQUINOLINE DERIVATIVE; CYTOCHROME P450 2D6 INHIBITOR; CYTOCHROME P450 3A INHIBITOR; HYDROXYPYRIDINES; PYRIDINE DERIVATIVE;

ANTIMALARIAL ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; CELL MEMBRANE PERMEABILITY; COMPUTER PROGRAM; CONTROLLED STUDY; COVALENT BOND; CRYOPRESERVATION; DEALKYLATION; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG STABILITY; DRUG TOXICITY; DRUG TRANSFORMATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; INCUBATION TIME; LIPOPHILICITY; LIVER CELL; LIVER CLEARANCE; METABOLIC CLEARANCE RATE; METABOLITE; MOLECULAR HYBRIDIZATION; PHARMACOPHORE; PHYSICAL CHEMISTRY; PLASMODIUM FALCIPARUM; PREDICTION; PROTEIN INDUCTION; TANDEM MASS SPECTROMETRY; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; CHEMISTRY; DRUG EFFECTS; DRUG INTERACTION; DRUG RESISTANCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MALARIA, FALCIPARUM; METABOLISM; PROCEDURES; TIME; VALIDATION STUDY;

AMINOQUINOLINES; ANTIMALARIALS; CHLOROQUINE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRYOPRESERVATION; CYTOCHROME P-450 CYP2D6 INHIBITORS; CYTOCHROME P-450 CYP3A INHIBITORS; DRUG INTERACTIONS; DRUG RESISTANCE; HEPATOCYTES; HUMANS; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM; PYRIDINES; TANDEM MASS SPECTROMETRY; TIME FACTORS;

EID: 84907168027     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2014.954547     Document Type: Article

References (33)

1. Snow RW, Guerra CA, Noor AM, et al. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005;434:214-17
2. World Health Organisation. Guidelines for the treatment of malaria. Geneva, Switzerland; 2010.p. 194. Available from: Http://whqlibdoc.who.int/publications/2010/9789241547925éng.pdf
3. Fidock DA. Drug discovery: Priming the antimalarial pipeline. Nature 2010;465:297-8
4. Dondorp AM, Fairhurst RM, Slutsker L, et al. The threat of artemisinin-resistant malaria. N Engl J Med 2011;365:1073-5
5. Cibulskis RE, Bell D, Christophel E-M, et al. Estimating Trends in the Burden of Malaria at Country Level. Am J Trop Med Hyg 2007;77:133-7
6. Wiwanitkit V. New emerging drugresistant malaria. Int J Gen Med 2010;3:327-9
7. Walsh JJ, Bell A. Hybrid drugs for malaria. Curr Pharm Des 2009;15:2970-85
8. Dechy-Cabaret O, Benoit-Vical F, Loup C, et al. Synthesis and antimalarial activity of trioxaquine derivatives. Chemistry 2004;10:1625-36
9. Opsenica I, Opsenica D, Lanteri CA, et al. New chimeric antimalarials with 4- aminoquinoline moiety linked to a tetraoxane skeleton. J Med Chem 2008;51:6216-19
10. Feng T-S, Guantai EM, Nell M, et al. Effects of highly active novel artemisininchloroquinoline hybrid compounds on beta-hematin formation, parasite morphology and endocytosis in Plasmodium falciparum. Biochem Pharmacol 2011;82:236-47
11. Andayi WA, Egan TJ, Gut J, et al. Synthesis, Antiplasmodial activity, and beta-hematin inhibition of hydroxypyridone-chloroquine hybrids. ACS Med Chem Lett 2013;4:642-6
12. Masimirembwa CM, Hasler JA, Johansson I. Inhibitory effects of antiparasitic drugs on cytochrome P450 2D6. Eur J Clin Pharmacol 1995;48:35-8
13. Bapiro TE, Egnell A-C, Hasler JA, Masimirembwa CM. Application of higher throughput screening (hts) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos 2001;29:30-5
14. Hershko C, Theanacho EN, Spira DT, et al. The effect of N-alkyl modification on the antimalarial activity of 3- hydroxypyridin-4-one oral iron chelators. Blood 1991;77:637-43
15. Kaschula CH, Egan TJ, Hunter R, et al. Structure and activity relationships in 4- aminoquinoline antiplasmodials. The role of the group at the 7-position. J Med Chem 2002;45:3531-9
16. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3-26
17. ChemAxon property calculator plugins. Available from: Http://www.chemaxon. com/marvin
18. de Aquino Ribeiro JA, de Campos LMM, Alves RJ, et al. Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis. J Pharm Biomed Anal 2007;43:298-303
19. Patel P, Osechinskiy S, Koehler J, et al. Micro parallel liquid chromatography for high-throughput compound purity analysis and early ADMET profiling. J Assoc Lab Autom 2004;9:185-91
20. MOKA. Available from: Http://www. moldiscovery.com/software/MOKA
21. Turbidimetric solubility assay. Available from: Http://www.cyprotex.com/admepk/physicochemical-properties/turbidimetricsolubility/
22. Vilá J, Obach R, Prieto R, Moreno J. Liquid chromatographic capacity factor as an indicator of lipophilicity in a series of betablocker drugs. Chromatographia 1986;22:48-50
23. Wiczling P, Kawczak P, Nasal A, Kaliszan R. Simultaneous Determination of pKa and Lipophilicity by Gradient RP HPLC. Anal Chem 2006;78:239-49
24. Masimirembwa C, Bredberg U, Andersson T. Metabolic stability for drug discovery and development: Pharmacokinetic and biochemical challenges. Clin Pharmacokinet 2003;42:515-28
25. Thompson T. Early ADME in support of drug discovery: The role of metabolic stability studies. Curr Drug Metab 2000;1:215-41
26. Barter Z, Bayliss M, Beaune P, et al. Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: Reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver. Curr Drug Metab 2007;8:33-45
27. Riley RJ, McGinnity DF, Austin RP. A unified model for predicting human hepatic, metabolic clearance from in vitro intrinsic clearance data in hepatocytes and microsomes. Drug Metab and Dispos 2005;33:1304-11
28. Houston BJ, Carlile DJ. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev 1997;29:891-922
29. Crespi CL, Miller VP, Penman W. Assays for cytochrome P450 inhibition. Anal Biochem 1997;248:188-90
30. Thelingwani RS, Zvada SP, Hugues D, et al. In vitro and in silico identification and characterisation of thiabendazole as a mechanism-based inhibitor of CYP1A2 and simulation of possible pharmacokinetic drug-drug interactions. Drug Metab Dispos 2009;37:1286-12894
31. Gleeson MP, Hersey A, Montanari D, Overington J. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat Rev Drug Discov 2011;10:197-208
32. Pang KS, Roland M. Hepatic clearance of drugs I: Theoretical considerations of a well-stirred and parallel-tube model. Influence of hepatic blood flow, plasma and blood cell binding and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokinet Biopharm 1977;5:625-53
33. Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine and amodiaquine: Clinical implications. Clin Pharmacokinet 1996;30:263-99