Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Aug;41(8):1658–1661. doi: 10.1128/aac.41.8.1658

Synthesis and antitrypanosomal activities of a series of 7-deaza-5'-noraristeromycin derivatives with variations in the cyclopentyl ring substituents.

K L Seley 1, S W Schneller 1, D Rattendi 1, S Lane 1, C J Bacchi 1
PMCID: PMC163980  PMID: 9257736

Abstract

Previous work in our laboratories has suggested that (+)-5'-nor-7-deazaaristeromycin (compound 1) may represent a prototype structure for a series of compounds with significant antitrypanosomal activities. To test this possibility, a series of derivatives of compound 1 with changes in the cyclopentyl substituents (compounds 3 to 10) have been studied. Although some growth activity was obtained with the L-like compound 5, related compounds 3 and 7 had little or no activity below 100 microM. D-like compounds 4 and 6 showed some activity at or below 100 microM, but the most interesting finding was that both the D- and L-like compounds having a methyl substituent on the 4' position were most active.

Full Text

The Full Text of this article is available as a PDF (193.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bacchi C. J., Brun R., Croft S. L., Alicea K., Bühler Y. In vivo trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob Agents Chemother. 1996 Jun;40(6):1448–1453. doi: 10.1128/aac.40.6.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bacchi C. J., Nathan H. C., Livingston T., Valladares G., Saric M., Sayer P. D., Njogu A. R., Clarkson A. B., Jr Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense. Antimicrob Agents Chemother. 1990 Jun;34(6):1183–1188. doi: 10.1128/aac.34.6.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bacchi C. J., Sufrin J. R., Nathan H. C., Spiess A. J., Hannan T., Garofalo J., Alecia K., Katz L., Yarlett N. 5'-Alkyl-substituted analogs of 5'-methylthioadenosine as trypanocides. Antimicrob Agents Chemother. 1991 Jul;35(7):1315–1320. doi: 10.1128/aac.35.7.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bitonti A. J., Byers T. L., Bush T. L., Casara P. J., Bacchi C. J., Clarkson A. B., Jr, McCann P. P., Sjoerdsma A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of S-adenosylmethionine decarboxylase. Antimicrob Agents Chemother. 1990 Aug;34(8):1485–1490. doi: 10.1128/aac.34.8.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hirumi H., Hirumi K. Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers. J Parasitol. 1989 Dec;75(6):985–989. [PubMed] [Google Scholar]
  6. Rupar M. J., Donovan W. P., Groat R. G., Slaney A. C., Mattison J. W., Johnson T. B., Charles J. F., Dumanoir V. C., de Barjac H. Two novel strains of Bacillus thuringiensis toxic to coleopterans. Appl Environ Microbiol. 1991 Nov;57(11):3337–3344. doi: 10.1128/aem.57.11.3337-3344.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Seley K. L., Schneller S. W., Rattendi D., Bacchi C. J. (+)-7-Deaza-5'-noraristeromycin as an anti-trypanosomal agent. J Med Chem. 1997 Feb 14;40(4):622–624. doi: 10.1021/jm9605039. [DOI] [PubMed] [Google Scholar]
  8. Van Nieuwenhove S. Advances in sleeping sickness therapy. Ann Soc Belg Med Trop. 1992;72 (Suppl 1):39–51. [PubMed] [Google Scholar]
  9. Wolfe M. S., Lee Y., Bartlett W. J., Borcherding D. R., Borchardt R. T. 4'-modified analogues of aristeromycin and neplanocin A: synthesis and inhibitory activity toward S-adenosyl-L-homocysteine hydrolase. J Med Chem. 1992 May 15;35(10):1782–1791. doi: 10.1021/jm00088a013. [DOI] [PubMed] [Google Scholar]
  10. Yarlett N., Quamina A., Bacchi C. J. Protein methylases in Trypanosoma brucei brucei: activities and response to DL-alpha-difluoromethylornithine. J Gen Microbiol. 1991 Mar;137(3):717–724. doi: 10.1099/00221287-137-3-717. [DOI] [PubMed] [Google Scholar]
  11. Yeh J. C., Borchardt R. T., Vedani A. A molecular model for the active site of S-adenosyl-L-homocysteine hydrolase. J Comput Aided Mol Des. 1991 Jun;5(3):213–234. doi: 10.1007/BF00124340. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES