Unknown

Dataset Information

0

Synthesis and evaluation of ?-thymidine analogues as novel antimalarials.


ABSTRACT: Plasmodium falciparum thymidylate kinase (PfTMPK) is a key enzyme in pyrimidine nucleotide biosynthesis. 3-Trifluoromethyl-4-chloro-phenyl-urea-?-thymidine has been reported as an inhibitor of Mycobacterium tuberculosis TMPK (MtTMPK). Starting from this point, we designed, synthesized and evaluated a number of thymidine analogues as antimalarials. Both 5'-urea-?- and ?-thymidine derivatives were moderate inhibitors of PfTMPK and furthermore showed moderate inhibition of parasite growth. The structure of several enzyme-inhibitor complexes provides a basis for improved inhibitor design. However, we found that certain 5'-urea-?-thymidine analogues had antimalarial activity where inhibition of PfTMPK is not the major mode of action. Optimization of this series resulted in a compound with potent antimalarial activity (EC(50) = 28 nM; CC(50) = 29 ?M).

SUBMITTER: Cui H 

PROVIDER: S-EPMC3530961 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

1994-01-01 | S-EPMC1137220 | BioStudies
1000-01-01 | S-EPMC1192817 | BioStudies
2018-01-01 | S-EPMC5826100 | BioStudies
2012-07-19 | E-GEOD-39485 | ArrayExpress
2012-01-01 | S-EPMC3349818 | BioStudies
2004-01-01 | S-EPMC523447 | BioStudies
1000-01-01 | S-EPMC5098533 | BioStudies
2012-01-01 | S-EPMC3361392 | BioStudies
1000-01-01 | S-EPMC3265284 | BioStudies
1000-01-01 | S-EPMC2440361 | BioStudies