7-Deaza-6-benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: Activities and selective toxicities

Biochemical Pharmacology

Volumn 76, Issue 8, 2008, Pages 958-966

  Al Safarjalani, Omar N ^a   Rais, Reem H ^a   Ah Kim, Young ^b   Chu, Chung K ^b   Naguib, Fardos N M ^a   el Kouni, Mahmoud H ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b UNIVERSITY OF GEORGIA   (United States)

Author keywords

7 Deaza 6 benzylthioinosine analogues; Adenosine kinase; Chemotherapy; Subversive substrates; Toxoplasma

Indexed keywords

6 BENZYLTHIOINOSINE; 7 DEAZA 6 (4 CYANOBENZYLTHIO)INOSINE; 7 DEAZA 6 (4 METHOXYBENZYLTHIO)INOSINE; 7 DEAZA 6 (4 METHOXYCARBONYLBENZYLTHIO)INOSINE; 7 DEAZA 6 BENZYLTHIOINOSINE DERIVATIVE; ADENOSINE; ADENOSINE KINASE; ANTIPROTOZOAL AGENT; INOSINE DERIVATIVE; LIGAND; PHENYL GROUP; TUBERCIDIN; UNCLASSIFIED DRUG;

ANTIPROTOZOAL ACTIVITY; ARTICLE; BINDING AFFINITY; CULTURE MEDIUM; DRUG EFFECT; DRUG EFFICACY; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME BINDING; ENZYME SUBSTRATE COMPLEX; FIBROBLAST; HUMAN; HUMAN CELL; IC 50; MONOLAYER CULTURE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; TOXOPLASMA GONDII;

ADENOSINE KINASE; ANIMALS; ANTIPROTOZOAL AGENTS; FIBROBLASTS; FORESKIN; HUMANS; INFANT, NEWBORN; MALE; PROTOZOAN PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; THIOINOSINE; TOXOPLASMA; TOXOPLASMOSIS;

EID: 52949153269     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2008.07.035     Document Type: Article

References (21)

1. Dubey J.P., and Beattie C.P. Toxoplasmosis of animals and man (1988), CRC Press, Boca Raton, FL
2. Luft B.J. Toxoplasma gondii. In: Walzer P.D., and Genta R.M. (Eds). Parasitic infections in the compromised host (1989), Marcel Dekker, New York 179-279
3. Remington J.S., McLeond R., and Desmonts G. Toxoplasmosis. In: Remington J.S., and Klein J.O. (Eds). Infectious diseases of the fetus and newborn infant (1995), W.B. Saunders Company, Philadelphia 140-267
4. Subauste C.S., and Remington J.S. Immunity to Toxoplasma gondii. Curr Opin Immunol 5 (1993) 532-537
5. Wong S., and Remington J.S. Biology of Toxoplasma gondii. AIDS 7 (1993) 299-316
6. el Kouni M.H. Potential chemotherapeutic targets in the purine metabolism of parasites. Pharmacol Therapeut 99 (2003) 283B-309
7. el Kouni M.H. Adenosine metabolism in Toxoplasma gondii: potential targets for chemotherapy. Curr Pharm Des 13 (2007) 581-597
8. Pfefferkorn E.R., and Pfefferkorn L.C. The biochemical basis for resistance to adenine arabinoside in a mutant of Toxoplasma gondii. J Parasitol 64 (1978) 486-492
9. Krug E.C., Marr J.J., and Berens R.L. Purine metabolism in Toxoplasma gondii. J Biol Chem 264 (1989) 10601-10607
10. Iltzsch M.H., Uber S.S., Tankersley K.O., and el Kouni M.H. Structure activity relationship for the binding of nucleoside ligands to adenosine kinase from Toxoplasma gondii. Biochem Pharmacol 49 (1995) 1501-1512
11. Yadav V., Chu C.K., Rais R.H., Al Safarjalani O.N., Guarcello V., Naguib F.N.M., et al. Synthesis, biological activity and molecular modeling of 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase. J Med Chem 47 (2004) 1987-1996
12. Kim Y.A., Sharon A., Chu C.K., Rais R.H., Al Safarjalani O.N., Naguib F.N.M., et al. Structure-activity relationships of 7-deaza-6-benzylthioinosine analogues as ligands of Toxoplasma gondii adenosine kinase. J Med Chem 51 (2008) 3934-3945
13. el Kouni M.H., Guarcello V., Al Safarjalani O.N., and Naguib F.N.M. Metabolism and selective toxicity of 6-nitrobenzylthioinosine in Toxoplasma gondii. Antimicrob agents Chemother 43 (1999) 2437-2443
14. Rais R.H., Al Safarjalani O.N., Yadav V., Guarcello V., Kirk M., Chu C.K., et al. 6-Benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: activities and selective toxicities. Biochem Pharmacol 69 (2005) 1409-1419
15. Al Safarjalani O.N., Naguib F.N.M., and el Kouni M.H. Uptake of nitrobenzylthioinosine and purine β-l-nucleosides by intracellular Toxoplasma gondii. Antimicrob Agents Chemother 47 (2003) 3247-3251
16. Gupte A., Buolamwini J.K., Yadav V., Chu C.K., Naguib F.N.M., and el Kouni M.H. 6-Benzylthioinosine analogues: promising anti-toxoplasmic agents as inhibitors of the mammalian nucleoside transporter ENT1 (es). Biochem Pharmacol 71 (2005) 69-73
17. Sullivan W.J., Chiang C.W., Wilson C.M., Naguib F.N.M., el Kouni M.H., Donald R.G.K., et al. Insertional tagging and cloning of at least two loci associated with resistance to adenine arabinoside in Toxoplasma gondii and cloning of the adenosine kinase locus. Mol Biochem Parasitol 103 (1999) 1-14
18. Zhang Y., el Kouni M.H., and Ealick S.E. Structure of Toxoplasma gondii adenosine kinase in complex with an ATP analog at 1.1 Å resolution. Acta Crystallogr D D62 (2006) 142-145
19. 6-benzyladenosine analogues as potential anti-toxoplasma agents. Biochem Pharmacol 73 (2007) 1558-1572
20. Pfefferkorn E.R., and Pfefferkorn L.C. Specific labeling of intracellular Toxoplasma gondii with uracil. J Protozool 4 (1977) 449-453
21. Cha S. Kinetics of enzyme reactions with competing alternative substrates. Mol Pharmacol 4 (1968) 621-629